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Kwofie, Samuel K., Emmanuel Broni, Bismark Dankwa, Kweku S. Enninful, Joshua Teye, Cedar R. Davidson, Josephine B. Nimely i in. "Review of Atypical Organometallic Compounds as Antimalarial Drugs". Journal of Chemistry 2020 (20.05.2020): 1–9. http://dx.doi.org/10.1155/2020/9414093.
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Organometallic compounds are molecules that contain at least one metal-carbon bond. Due to resistance of the Plasmodium parasite to traditional organic antimalarials, the use of organometallic compounds has become widely adopted in antimalarial drug discovery. Ferroquine, which was developed due to the emergence of chloroquine resistance, is currently the most advanced organometallic antimalarial drug and has paved the way for the development of new organometallic antimalarials. In this review, a general overview of organometallic antimalarial compounds and their antimalarial activity in comparison to purely organic antimalarials are presented. Furthermore, recent developments in the field are discussed, and future applications of this emerging class of therapeutics in antimalarial drug discovery are suggested.
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Esdaile, John M. "The Efficacy of Antimalarials in Systemic Lupus Erythematosus". Lupus 2, nr 1_suppl (luty 1993): 3–8. http://dx.doi.org/10.1177/0961203393002001021.
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The use of antimalarial drugs to treat systemic lupus erythematosus (SLE) is reviewed regarding their value in SLE of mild-to-moderate disease activity, as corticosteroid-sparing agents, and as an adjunctive therapy in severe SLE. A retrospective controlled study of a variety of antimalarials and a randomized discontinuation trial of hydroxychloroquine support the considerable clinical belief that antimalarials are of benefit in mild-to-moderate SLE. Anecdotal reports and the opinion of experienced clinicians suggest that antimalarials permit the use of lower doses of corticosteroids. No controlled study has confirmed a corticosteroid-sparing role for antimalarials, although no controlled study has been conducted specifically to address this hypothesis. The data on antimalarials in severe SLE are scant. Antimalarials are likely effective in at least a subgroup of SLE patients with mild-to-moderate disease activity. Whether these agents are corticosteroid sparing and prevent severe disease exacerbations is unproven. Given the low toxicity of antimalarials, further studies are clearly warranted.
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Opsenica, Igor, Dejan Opsenica, Milka Jadranin, Kirsten Smith, Wilbur Milhous, Manolis Stratakis i Bogdan Solaja. "On peroxide antimalarials". Journal of the Serbian Chemical Society 72, nr 12 (2007): 1181–90. http://dx.doi.org/10.2298/jsc0712181o.
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Several dicyclohexylidene tetraoxanes were prepared in order to gain a further insight into structure-activity relationship of this kind of antimalarials. The tetraoxanes 2-5, obtained as a cis/trans mixture, showed pronounced antimalarial activity against Plasmodium falciparum chloroquine susceptible D6, chloroquine resistant W2 and multidrug-resistant TM91C235 (Thailand) strains. They have better than or similar activity to the corresponding desmethyl dicyclohexylidene derivatives. Two chimeric endoperoxides with superior antimalarial activity to the natural product ascaridole were also synthesized.
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Evans, Daniel R., Colleen R. Higgins, Sarah K. Laing, Phyllis Awor i Sachiko Ozawa. "Poor-quality antimalarials further health inequities in Uganda". Health Policy and Planning 34, Supplement_3 (1.12.2019): iii36—iii47. http://dx.doi.org/10.1093/heapol/czz012.
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Abstract Substandard and falsified medications are a major threat to public health, directly increasing the risk of treatment failure, antimicrobial resistance, morbidity, mortality and health expenditures. While antimalarial medicines are one of the most common to be of poor quality in low- and middle-income countries, their distributional impact has not been examined. This study assessed the health equity impact of substandard and falsified antimalarials among children under five in Uganda. Using a probabilistic agent-based model of paediatric malaria infection (Substandard and Falsified Antimalarial Research Impact, SAFARI model), we examine the present day distribution of the burden of poor-quality antimalarials by socio-economic status and urban/rural settings, and simulate supply chain, policy and patient education interventions. Patients incur US$26.1 million (7.8%) of the estimated total annual economic burden of substandard and falsified antimalarials, including $2.3 million (9.1%) in direct costs and $23.8 million (7.7%) in productivity losses due to early death. Poor-quality antimalarials annually cost $2.9 million to the government. The burden of the health and economic impact of malaria and poor-quality antimalarials predominantly rests on the poor (concentration index −0.28) and rural populations (98%). The number of deaths among the poorest wealth quintile due to substandard and falsified antimalarials was 12.7 times that of the wealthiest quintile, and the poor paid 12.1 times as much per person in out-of-pocket payments. Rural populations experienced 97.9% of the deaths due to poor-quality antimalarials, and paid 10.7 times as much annually in out-of-pocket expenses compared with urban populations. Our simulations demonstrated that interventions to improve medicine quality could have the greatest impact at reducing inequities, and improving adherence to antimalarials could have the largest economic impact. Substandard and falsified antimalarials have a significant health and economic impact, with greater burden of deaths, disability and costs on poor and rural populations, contributing to health inequities in Uganda.
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Agbo, Chinonyelum Emmanuel, Uzochukwu Emmanuel Chima, Sunday Chibueze Ogbobe, Faith Olanrewaju Omotayo i Success Chekwubechukwu David. "Transdermal antimalarial drug delivery to improve poor adherence to antimalarials: A new light at the end of the tunnel". American Journal of Biopharmacy and Pharmaceutical Sciences 3 (2.12.2023): 4. http://dx.doi.org/10.25259/ajbps_14_2023.
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Malaria, a perilous disease caused by Plasmodium parasites and characterized by a substantial mortality rate, has persistently posed as a global health challenge. Conventional antimalarial formulations, although effective, grapple with issues surrounding their bioavailability and palatability, and potentially hampering patient adherence and inadvertently fueling drug resistance and poor treatment outcomes. This paper meticulously delves into the predicaments associated with prevailing antimalarial delivery methods – oral, intravenous, and intramuscular. The paper navigates through the compelling merits of the transdermal pathway, drawing inspiration from its triumphant deployment in other medical realms. The investigation extends to encompass preclinical inquiries dedicated to exploring the transdermal administration of antimalarials. Transdermal antimalarials have shown complete suppression and elimination of Plasmodium parasites, as suggested by the preclinical studies. These preclinical studies emerge as a beacon of hope, exhibiting heightened bioavailability, enhanced safety margins, and notable cost-effectiveness when compared with oral antimalarials. Moreover, this innovative avenue for drug delivery not only offers convenience but also holds the potential to be a transformative solution to the adherence problems of traditional antimalarials, which currently afflicts standard therapeutic options.
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Zieliński, Ewa, Marek Kowalczyk, Karolina Osowiecka, Łukasz Klepacki, Łukasz Dyśko i Katarzyna Wojtysiak. "The Problem of Antimalarial-Drug Abuse by the Inhabitants of Ghana". Medicina 59, nr 2 (29.01.2023): 257. http://dx.doi.org/10.3390/medicina59020257.
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Introduction: Malaria is still a huge social and economic health problem in the world. It especially affects the developing countries of Africa. A particular problem is the misuse and abuse of over-the-counter antimalarials. This problem could lead to the emergence of drug-resistant strains and the subsequent elimination of more antimalarials from the list of effective antimalarials in Ghana. Methods: During the implementation of the study, an original questionnaire was used to collect data among Ghanaians on their knowledge of malaria, attitude towards antimalarials and their use of antimalarials. Results: The proportion in the analyzed subgroups was compared using the chi-square test. The analysis was conducted using TIBCO Software Inc., Krakow, Poland (2017) and Statistica (data analysis software system), version 13. In total, 86.29% of respondents knew the symptoms of malaria (p = 0.02) and 57.2% knew the cause of malaria (p < 0.001). Respondents with higher education were significantly more likely to know the symptoms of malaria (96%) p < 0.001. In the study group, only 74.59% of the respondents consulted medical personnel before taking the antimalarial drug (p = 0.51) and only 14.2% of the remaining respondents performed a rapid diagnostic test for malaria. Conclusions: The awareness of Accra and Yendi native inhabitants about the causes and symptoms of malaria and alternative ways of prevention is quite high. People’s education very significantly influences the way Accra residents deal with suspected malaria. Widespread public education and awareness and accessibility to places where antimalarial drugs are sold play a very important role in the proper use of antimalarial drugs.
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Yousif, M. A., i A. A. Adeel. "Antimalarials prescribing patterns in Gezira state: precepts and practices". Eastern Mediterranean Health Journal 6, nr 5-6 (15.12.2000): 939–47. http://dx.doi.org/10.26719/2000.6.5-6.939.
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A longitudinal pharmacoepidemiological study on prescribing patterns of antimalarials was conducted in Gezira State, Sudan. Different core drug prescribing indicators were identified, measured and correlated. Chloroquine and quinine were the most frequently prescribed antimalaria drugs but in 44.7% of cases, the dosage was inappropriate and did not conform to standard regimens. Due to variable and unmonitored patterns of drug resistance, most medical practitioners in Sudan tend to follow their own protocols to treat severe cases of malaria rather than conforming to standard regimens. We attribute the emergence of a high rate of resistance to malaria chemotherapy to such practices. We recommend interventions to ensure rational prescribing, and call for the formulation of a national antimalarial drugs policy.
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Heppner, DG, PE Hallaway, GJ Kontoghiorghes i JW Eaton. "Antimalarial properties of orally active iron chelators". Blood 72, nr 1 (1.07.1988): 358–61. http://dx.doi.org/10.1182/blood.v72.1.358.358.
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Abstract The appearance of widespread multiple drug resistance in human malaria has intensified the search for new antimalarial compounds. Metal chelators, especially those with high affinity for iron, represent one presently unexploited class of antimalarials. Unfortunately the use of previously identified chelators as antimalarials has been precluded by their toxicity and, in the case of desferrioxamine, the necessity for parenteral administration. The investigators now report that a new class of orally active iron chelators, namely the derivatives of alpha- ketohydroxypyridines (KHPs), are potent antimalarials against cultured Plasmodium falciparum. The KHPs evidently exert this effect by sequestering iron because a preformed chelator:iron complex has no antimalarial action. The pool(s) of iron being sequestered by the chelators have not been identified but may not include serum transferrin. Preincubation of human serum with KHPs followed by removal of the drug results in the removal of greater than 97% of total serum iron. Nonetheless, this serum effectively supports the growth of P falciparum cultures. Therefore the KHPs may exert antimalarial effect through chelation of erythrocytic rather than serum iron pool(s). The investigators conclude that these powerful, orally active iron chelators may form the basis of a new class of antimalarial drugs.
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Heppner, DG, PE Hallaway, GJ Kontoghiorghes i JW Eaton. "Antimalarial properties of orally active iron chelators". Blood 72, nr 1 (1.07.1988): 358–61. http://dx.doi.org/10.1182/blood.v72.1.358.bloodjournal721358.
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The appearance of widespread multiple drug resistance in human malaria has intensified the search for new antimalarial compounds. Metal chelators, especially those with high affinity for iron, represent one presently unexploited class of antimalarials. Unfortunately the use of previously identified chelators as antimalarials has been precluded by their toxicity and, in the case of desferrioxamine, the necessity for parenteral administration. The investigators now report that a new class of orally active iron chelators, namely the derivatives of alpha- ketohydroxypyridines (KHPs), are potent antimalarials against cultured Plasmodium falciparum. The KHPs evidently exert this effect by sequestering iron because a preformed chelator:iron complex has no antimalarial action. The pool(s) of iron being sequestered by the chelators have not been identified but may not include serum transferrin. Preincubation of human serum with KHPs followed by removal of the drug results in the removal of greater than 97% of total serum iron. Nonetheless, this serum effectively supports the growth of P falciparum cultures. Therefore the KHPs may exert antimalarial effect through chelation of erythrocytic rather than serum iron pool(s). The investigators conclude that these powerful, orally active iron chelators may form the basis of a new class of antimalarial drugs.
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Tang, Yu-Qing, Qian Ye, He Huang i Wei-Yi Zheng. "An Overview of Available Antimalarials: Discovery, Mode of Action and Drug Resistance". Current Molecular Medicine 20, nr 8 (29.12.2020): 583–92. http://dx.doi.org/10.2174/1566524020666200207123253.
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: Malaria is one of the three most deadly infectious diseases in the world and seriously endangers human health and life. To reduce the public health burden of this disease, scientists have focused on the discovery and development of effective antimalarial drugs, from quinine and chloroquine to antifolates and artemisinin and its derivatives, which all play a profound role in the treatment of malaria. However, drugresistant strains of Plasmodium falciparum have emerged due to frequent use of antimalarials and have become increasingly resistant to existing antimalarial drugs, causing disastrous consequences in the world. In particular, artemisinin resistance is of greatest concern which was reported in 2008. Resistance to artenisinins has been a major obstacle for malaria control, and current efforts to curb artemisinin resistance have not been successful. Based on the current situation, it is urgent to develop more effective new antimalarials with distinct targets from conventional antimalarials in the world, which could facilitate to minimize the phenomenon of drug resistance. This review aims to summarize different kinds of antimalarial therapeutic efficacy, mechanisms of action and resistance, and proposes new solutions aiming towards further improvement of malaria elimination.
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Triatmoko, Bawon, Dwi Koko Pratoko, Antonius Nugraha Widhi Pratama, Yoshinta Debi Purnomo, Tinton Agung Laksono i Ari Satia Nugraha. "Preliminary Study on Antimalarial Agent From Indonesian Swietenia Mahagoni and Kibatalia Arborea". Proceedings of the International Conference on Green Technology 10 (31.12.2019): 13. http://dx.doi.org/10.18860/icgt.v10i0.1113.
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Malaria is a global public health concern due to the increase of resistance to antimalarials, therefore the search for new antimalarials is of importance. This study was conducted to explore the antimalarial activity of Swietenia mahagoni and Kibatalia arborea in the form of crude methanolic extract. The plants were collected from Klaten-Central Java, and Batu-East Java, Indonesia. In vitro antimalarial assay was done against Plasmodium falciparum. Phytochemical studies were done chemically using Dragendorff’s reagent and spectroscopically using the 1H-NMR technique. Results show that the extract indicated positive antimalarial activity. Preliminary chemotype studies revealed the extract constitutes alkaloid compounds in which proton NMR indicated a typical aromatic alkaloid molecular structure. In conclusion, S. mahagoni K. arborea are potential for an antimalarial agent and further studies are necessary to obtain the bioactive compounds responsible for the claimed activity.
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Creek, Darren J., Eileen Ryan, William N. Charman, Francis C. K. Chiu, Richard J. Prankerd, Jonathan L. Vennerstrom i Susan A. Charman. "Stability of Peroxide Antimalarials in the Presence of Human Hemoglobin". Antimicrobial Agents and Chemotherapy 53, nr 8 (1.06.2009): 3496–500. http://dx.doi.org/10.1128/aac.00363-09.
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ABSTRACT Peroxide antimalarials, including artemisinin, are important for the treatment of multidrug-resistant malaria. These peroxides are known to react with iron or heme to produce reactive intermediates that are thought to be responsible for their antimalarial activities. This study investigated the potential interaction of selected peroxide antimalarials with oxyhemoglobin, the most abundant form of iron in the human body. The observed stability of artemisinin derivatives and 1,2,4-trioxolanes in the presence of oxyhemoglobin was in contrast to previous reports in the literature. Spectroscopic analysis of hemoglobin found it to be unstable under the conditions used for previous studies, and it appears likely that the artemisinin reactivity reported in these studies may be attributed to free heme released by protein denaturation. The stability of peroxide antimalarials with intact oxyhemoglobin, and reactivity with free heme, may explain the selective toxicity of these antimalarials toward infected, but not healthy, erythrocytes.
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Van Tyne, Daria, Alessandro D. Uboldi, Julie Healer, Alan F. Cowman i Dyann F. Wirth. "Modulation of PF10_0355 (MSPDBL2) Alters Plasmodium falciparum Response to Antimalarial Drugs". Antimicrobial Agents and Chemotherapy 57, nr 7 (15.04.2013): 2937–41. http://dx.doi.org/10.1128/aac.02574-12.
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ABSTRACTMalaria's ability to rapidly adapt to new drugs has allowed it to remain one of the most devastating infectious diseases of humans. Understanding and tracking the genetic basis of these adaptations are critical to the success of treatment and intervention strategies. The novel antimalarial resistance locusPF10_0355(Pfmspdbl2) was previously associated with the parasite response to halofantrine, and functional validation confirmed that overexpression of this gene lowered parasite sensitivity to both halofantrine and the structurally related antimalarials mefloquine and lumefantrine, predominantly through copy number variation. Here we further characterize the role ofPfmspdbl2in mediating the antimalarial drug response ofPlasmodium falciparum. Knockout ofPfmspdbl2increased parasite sensitivity to halofantrine, mefloquine, and lumefantrine but not to unrelated antimalarials, further suggesting that this gene mediates the parasite response to a specific class of antimalarial drugs. A single nucleotide polymorphism encoding a C591S mutation withinPfmspdbl2had the strongest association with halofantrine sensitivity and showed a high derived allele frequency among Senegalese parasites. Transgenic parasites expressing the ancestralPfmspdbl2allele were more sensitive to halofantrine and structurally related antimalarials than were parasites expressing the derived allele, revealing an allele-specific effect on drug sensitivity in the absence of copy number effects. Finally, growth competition experiments showed that under drug pressure, parasites expressing the derived allele ofPfmspdbl2outcompeted parasites expressing the ancestral allele within a few generations. Together, these experiments demonstrate that modulation ofPfmspdbl2affects malaria parasite responses to antimalarial drugs.
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Issaka, Mariama, Adamou Salissou, Ibrahim Arzika, Julia Guillebaud, Abani Maazou, Sabine Specht, Halima Zamanka i Thierry Fandeur. "Ex VivoResponses of Plasmodium falciparum Clinical Isolates to Conventional and New Antimalarial Drugs in Niger". Antimicrobial Agents and Chemotherapy 57, nr 7 (22.04.2013): 3415–19. http://dx.doi.org/10.1128/aac.02383-12.
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ABSTRACTLittle is known about resistance ofPlasmodium falciparumto antimalarials in Sahelian countries. Here we investigated the drug susceptibilities of fresh isolates collected in Niger post-deployment of artemisinin-based combination therapies (ACTs). We found that the parasites remained highly susceptible to new (dihydroartemisinin, lumefantrine, pyronaridine, and piperaquine) and conventional (amodiaquine and chloroquine) antimalarial drugs. The introduction of ACTs in 2005 and their further deployment nationwide have therefore not resulted in a decrease inP. falciparumsusceptibilities to these antimalarials.
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Egwu, Chinedu Ogbonnia, Nwogo Ajuka Obasi, Chinyere Aloke, Joseph Nwafor, Ioannis Tsamesidis, Jennifer Chukwu i Sunday Elom. "Impact of Drug Pressure versus Limited Access to Drug in Malaria Control: The Dilemma". Medicines 9, nr 1 (4.01.2022): 2. http://dx.doi.org/10.3390/medicines9010002.
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Malaria burden has severe impact on the world. Several arsenals, including the use of antimalarials, are in place to curb the malaria burden. However, the application of these antimalarials has two extremes, limited access to drug and drug pressure, which may have similar impact on malaria control, leading to treatment failure through divergent mechanisms. Limited access to drugs ensures that patients do not get the right doses of the antimalarials in order to have an effective plasma concentration to kill the malaria parasites, which leads to treatment failure and overall reduction in malaria control via increased transmission rate. On the other hand, drug pressure can lead to the selection of drug resistance phenotypes in a subpopulation of the malaria parasites as they mutate in order to adapt. This also leads to a reduction in malaria control. Addressing these extremes in antimalarial application can be essential in maintaining the relevance of the conventional antimalarials in winning the war against malaria.
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Nayak, V., i Jm Esdaile. "The efficacy of antimalarials in systemic lupus erythematosus". Lupus 5, nr 1_suppl (czerwiec 1996): 23–27. http://dx.doi.org/10.1177/0961203396005001061.
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The use of antimalarial drugs to treat systemic lupus erythematosus (SLE) is receiving increased attention. A retrospective controlled study suggested that antimalarials were useful in suppressing disease activity in SLE. A randomized discontinuation trial of hydroxychloroquine sulphate supported the clinical belief that antimalarials are of benefit in SLE of mild to moderate disease activity and might have a role as adjunctive therapy to protect against more severe relapses of SLE. A randomized trial of the ability of hydroxychloroquine sulphate to suppress articular manifestations of SLE demonstrated no consistent statistically significant benefit, although the sample size was small. Anecdotal reports and the experience of expert clinicians have suggested a corticosteroid sparing role for antimalarials, although no controlled study has been conducted to specifically address this hypothesis. Thus, the evidence favors a role for antimalarials in suppressing mild to moderate disease activity in SLE and possibly in preventing severe disease exacerbations. Their role as corticosteroid sparing agents in SLE is widely believed, but unproven.
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Manirakiza, Alexandre, Georges Soula, Remi Laganier, Elise Klement, Djibrine Djallé, Moyen Methode, Nestor Madji, Luc Salva Heredeïbona, Alain Le Faou i Jean Delmont. "Pattern of the Antimalarials Prescription during Pregnancy in Bangui, Central African Republic". Malaria Research and Treatment 2011 (15.07.2011): 1–4. http://dx.doi.org/10.4061/2011/414510.
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Introduction. The aim of this study was to identify the antimalarials prescribed during the pregnancy and to document their timing. Method. From June to September 2009, a survey was conducted on 565 women who gave birth in the Castors maternity in Bangui. The antenatal clinics cards were checked in order to record the types of antimalarials prescribed during pregnancy according to gestational age. Results. A proportion of 28.8% ANC cards contained at least one antimalarial prescription. The commonest categories of antimalarials prescribed were: quinine (56.7%), artemisinin-based combinations (26.8%) and artemisinin monotherapy (14.4%). Among the prescriptions that occurred in the first trimester of pregnancy, artemisinin-based combinations and artemisinin monotherapies represented the proportions of (10.9%) and (13.3%). respectively. Conclusion. This study showed a relatively high rate (>80%) of the recommended antimalarials prescription regarding categories of indicated antimalarials from national guidelines. But, there is a concern about the prescription of the artemisinin derivatives in the first trimester of pregnancy, and the prescription of artemisinin monotherapy. Thus, the reinforcement of awareness activities of health care providers on the national malaria treatment during pregnancy is suggested.
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Duncan, MR, i HA Capell. "The use of antimalarials in combination with other disease modifying agents in RA – the British experience". Lupus 5, nr 1_suppl (czerwiec 1996): 50–58. http://dx.doi.org/10.1177/0961203396005001121.
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Antimalarial drugs are effective disease modifying agents in RA with a low incidence of serious toxic effects. Recently, combinations of second-line agents have been used in RA in attempts to treat patients with no response to a number of single agents, or suboptimal response to a single agent. Combinations of drugs have been selected for maximum efficacy and minimum toxicity, but clinical trials are difficult to design and interpret. In particular, ensuring adequate power to detect small differences in response poses a major problem. Antimalarials are an attractive choice for combination therapy due to their efficacy, mechanisms of action and toxicity profile. In this review, the evidence for the use of antimalarials in combination in RA is examined. No advantage has been shown in combining antimalarials with gold, penicillamine or sulphasalazine compared with monotherapeutic regimens. There is some evidence to suggest a beneficial combination of antimalarials with methotrexate, but this is as yet inconclusive. Open non-randomised uncontrolled studies have shown that antimalarials combined with cytotoxic agents are effective but highly toxic. The authors conclude that there is little good evidence to support the introduction of combination second-line drug therapy for RA into widespread therapeutic use.
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Ezedom, Theresa, Innocent Onyesom, Prosper Ejiro Awhin, Chinwendu Obogheneophruhe Elu i Joy Onyewonuwa Acha. "PROFILING OF PHYLLANTHUS AMARUS PHYTOCHEMICAL CONSTITUENTS AND EVALUATION OF ASSOCIATED ANTIMALARIAL ACTIVITY AND ANTIOXIDANT POTENTIAL IN EXPERIMENTAL MICE". EPH - International Journal of Biological & Pharmaceutical Science 9, nr 1 (11.09.2023): 4–12. http://dx.doi.org/10.53555/eijbps.v9i1.40.
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The failing curative ability of antimalarials has prompted an open discussion for the use of antioxidants in combination with antimalarials for effective chemotherapy. This study profiled the phytochemical constituents of Phyllanthus amarus and evaluated their antimalarial and antioxidant activities. Phytochemical screening, antimalarial and acute oral toxicity were determined according to standard procedures. Blood antioxidant activity was assessed by measuring antioxidant enzymes and nitric oxide (NO), concentrations of malarial infected mice treated with P. amarus phytochemicals. Alkaloids, the most abundant phytochemical, demonstrated the highest malarial parasite chemosuppression and greatly improved NO concentration in infected mice. However, flavonoid extract demonstrated the highest antioxidant potential with most significant impact on catalase and malondialdehyde activity. Alkaloid may function as antimalarial agent by inhibiting haem polymerization to hemozoin as judged by its increased effect on NO concentration which bears an reverse relationship with hemozoin.
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Fang, Yaqun, Xiaoqin He, Pengcheng Zhang, Chuanbin Shen, James Mwangi, Cheng Xu, Guoxiang Mo, Ren Lai i Zhiye Zhang. "In Vitro and In Vivo Antimalarial Activity of LZ1, a Peptide Derived from Snake Cathelicidin". Toxins 11, nr 7 (30.06.2019): 379. http://dx.doi.org/10.3390/toxins11070379.
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Antimalarial drug resistance is an enormous global threat. Recently, antimicrobial peptides (AMPs) are emerging as a new source of antimalarials. In this study, an AMP LZ1 derived from snake cathelicidin was identified with antimalarial activity. In the in vitro antiplasmodial assay, LZ1 showed strong suppression of blood stage Plasmodium falciparum (P. falciparum) with an IC50 value of 3.045 μM. In the in vivo antiplasmodial assay, LZ1 exerted a significant antimalarial activity against Plasmodium berghei (P. berghei) in a dose- and a time- dependent manner. In addition, LZ1 exhibited anti-inflammatory effects and attenuated liver-function impairment during P. berghei infection. Furthermore, by employing inhibitors against glycolysis and oxidative phosphorylation in erythrocytes, LZ1 specifically inhibited adenosine triphosphate (ATP) production in parasite-infected erythrocyte by selectively inhibiting the pyruvate kinase activity. In conclusion, the present study demonstrates that LZ1 is a potential candidate for novel antimalarials development.
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Fernández, Diana, César Segura, Margarita Arboleda, Giovanny Garavito, Silvia Blair i Adriana Pabón. "In VitroSusceptibility of Plasmodium vivax to Antimalarials in Colombia". Antimicrobial Agents and Chemotherapy 58, nr 11 (11.08.2014): 6354–59. http://dx.doi.org/10.1128/aac.03191-14.
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ABSTRACTThein vitrosusceptibilities of 30 isolates ofPlasmodium vivaxto a number of antimalarials (chloroquine [CQ], mefloquine, amodiaquine, quinine, and artesunate [AS]) were evaluated. The isolates came from the region of Urabá in Colombia, in which malaria is endemic, and were evaluated by the schizont maturation test. The 50% inhibitory concentration (IC50) was 0.6 nM (95% confidence interval [CI], 0.3 to 1.0 nM) for artesunate, 8.5 nM (95% CI, 5.6 to 13.0 nM) for amodiaquine, 23.3 nM (95% CI, 12.4 to 44.1 nM) for chloroquine, 55.6 nM (95% CI, 36.8 to 84.1 nM) for mefloquine, and 115.3 nM (95% CI, 57.7 to 230.5 nM) for quinine. The isolates were classified according to whether the initial parasites were mature or immature trophozoites (Tfz). It was found that the IC50s for chloroquine and artesunate were significantly different in the two aforementioned groups (P< 0.001). The IC50s of CQ and AS were higher in the isolates from mature Tfz (CQ, 39.3 nM versus 17 nM; AS, 1.4 nM versus 0.3 nM), and 10% of the isolates showed lower susceptibilities to one of the antimalarial drugs, 13.3% to two antimalarial drugs, and 3.3% to more than three antimalarial drugs. It should be highlighted that despite the extensive use of chloroquine in Colombia,P. vivaxcontinues to be susceptible to antimalarials. This is the first report, to our knowledge, showingin vitrosusceptibilities ofP. vivaxisolates to antimalarials in Colombia.
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MODUPE IRETIOLA BUILDERS. "The potency of plant antimalarial". World Journal of Biology Pharmacy and Health Sciences 12, nr 1 (30.10.2022): 190–99. http://dx.doi.org/10.30574/wjbphs.2022.12.1.0113.
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Malaria has remained a major cause of morbidity and mortality in all parts of the world. It is associated with high economic burden on the nation, high prevalence of mortality in children, pregnant women and non-immune individuals, thus malaria is a global public health problem. This protozoan infection is mainly characterized by fever, pains, loss of appetite and anaemia, researchers had discovered potent antimalarial drugs mainly from plant sources in order to overcome resistance of antimalarials, vectors, inability to develop malarial vaccines and also toxic effects of conventional antimalarial drugs. Antimalarials obtained from plants have significant roles in drug discovery and development for the treatment of fever, pains, inflammation as well as Plasmodium falciparum infection, therefore this review focuses on the analgesics, antipyretics and anti-inflammatory activities as well as antiplasmodial activities of plants.
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Piscianz, Elisa, Eva Cuzzoni, Rajan Sharma, Alessandra Tesser, Pooja Sapra i Alberto Tommasini. "Reappraisal of Antimalarials in Interferonopathies: New Perspectives for Old Drugs". Current Medicinal Chemistry 25, nr 24 (4.07.2018): 2797–810. http://dx.doi.org/10.2174/0929867324666170911162331.
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The story of antimalarials as antinflammatory drugs dates back several centuries. Chinin, the extract of the Cinchona bark, has been exploited since the 18th century for its antimalarial and antifebrile properties. Later, during the Second World War, the broad use of antimalarials allowed arguing their antirheumatic effect on soldiers. Since then, these drugs have been broadly used to treat Systemic Lupus Erythematosus, but, only recently, have the molecular mechanisms of action been partly clarified. <p> Inhibitory action on vacuole function and trafficking has been considered for decades the main mechanism of the action of antimalarials, affecting the activation of phagocytes and dendritic cells. In addition, chloroquine is also known as a potent inhibitor of autophagy, providing another possible explanation of its antinflammatory action. However, much attention has been recently devoted to the action of antimalarials on the so-called cGASSTING pathway leading from the sensing of cytoplasmic nucleic acids to the production of type I interferons. <p> This pathway is a fundamental mechanism of host defence, since it is able to detect microbial DNA and induce the type I interferon-mediated immune response. Of note, genetic defects in the degradation of nucleic acids lead to inappropriate cGAS-STING activation and inflammation. These disorders, called type I interferonopathies, represent a valuable model to study the antinflammatory potential of antimalarials. <p> We will discuss possible development of antimalarials to improve the treatment of type I interferonopathies and likely multifactorial disorders characterised by interferon inflammation, such as Systemic Lupus Erythematosus.
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Dembele, Laurent, Yaw Aniweh, Nouhoum Diallo, Fanta Sogore, Cheick Papa Oumar Sangare, Aboubecrin Sedhigh Haidara, Aliou Traore i in. "Plasmodium malariae and Plasmodium falciparum comparative susceptibility to antimalarial drugs in Mali". Journal of Antimicrobial Chemotherapy 76, nr 8 (22.05.2021): 2079–87. http://dx.doi.org/10.1093/jac/dkab133.
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Abstract Objectives To evaluate Plasmodium malariae susceptibility to current and lead candidate antimalarial drugs. Methods We conducted cross-sectional screening and detection of all Plasmodium species malaria cases, which were nested within a longitudinal prospective study, and an ex vivo assessment of efficacy of a panel of antimalarials against P. malariae and Plasmodium falciparum, both PCR-confirmed mono-infections. Reference compounds tested included chloroquine, lumefantrine, artemether and piperaquine, while candidate antimalarials included the imidazolopiperazine GNF179, a close analogue of KAF156, and the Plasmodium phosphatidylinositol-4-OH kinase (PI4K)-specific inhibitor KDU691. Results We report a high frequency (3%–15%) of P. malariae infections with a significant reduction in ex vivo susceptibility to chloroquine, lumefantrine and artemether, which are the current frontline drugs against P. malariae infections. Unlike these compounds, potent inhibition of P. malariae and P. falciparum was observed with piperaquine exposure. Furthermore, we evaluated advanced lead antimalarial compounds. In this regard, we identified strong inhibition of P. malariae using GNF179, a close analogue of KAF156 imidazolopiperazines, which is a novel class of antimalarial drug currently in clinical Phase IIb testing. Finally, in addition to GNF179, we demonstrated that the Plasmodium PI4K-specific inhibitor KDU691 is highly inhibitory against P. malariae and P. falciparum. Conclusions Our data indicated that chloroquine, lumefantrine and artemether may not be suitable for the treatment of P. malariae infections and the potential of piperaquine, as well as new antimalarials imidazolopiperazines and PI4K-specific inhibitor, for P. malariae cure.
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Sukhoverkov, Kirill V., Maxime G. Corral, Julie Leroux, Joel Haywood, Philipp Johnen, Trevor Newton, Keith A. Stubbs i Joshua S. Mylne. "Improved herbicide discovery using physico-chemical rules refined by antimalarial library screening". RSC Advances 11, nr 15 (2021): 8459–67. http://dx.doi.org/10.1039/d1ra00914a.
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Trawling hundreds of antimalarials for herbicides, we develop a weighted scoring system for the phys-chem ‘rules’ of herbicide-likeness. Using this, we discover the antimalarial MMV1206386 is herbicidal via a novel mode of action.
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Aksic, Jelena, Marija Gencic i Niko Radulovic. "Recent updates in the development of mettallocenes with antimalarial activity". Facta universitatis - series: Physics, Chemistry and Technology 18, nr 1 (2020): 1–37. http://dx.doi.org/10.2298/fupct2001001a.
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Great progress in the fight against malaria has been made in the last decade. Nevertheless, the development of resistance to almost all commonly used antimalarial drugs poses a major threat to the sustainability of this progress and highlights the need for the discovery of novel potent and inexpensive antimalarials to stay one step ahead. After the finding of ferrocene-containing analog of chloroquine - ferroquine, that can overcome Plasmodium resistance, a ?big-bang? in the metallocene antimalarials research has occurred. This review describes in detail the most recent advances in this important field of medicinal chemistry. Even though it is quite hard to beat ferroquine, it seems that this could be succeeded by suitable modifications in the structure of ferroquine, by the introduction of ? second metal center or through joining metallocenes with two or more proven antimalarial motifs into a single molecule.
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Creek, Darren J., William N. Charman, Francis C. K. Chiu, Richard J. Prankerd, Yuxiang Dong, Jonathan L. Vennerstrom i Susan A. Charman. "Relationship between Antimalarial Activity and Heme Alkylation for Spiro- and Dispiro-1,2,4-Trioxolane Antimalarials". Antimicrobial Agents and Chemotherapy 52, nr 4 (11.02.2008): 1291–96. http://dx.doi.org/10.1128/aac.01033-07.
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ABSTRACT The reaction of spiro- and dispiro-1,2,4-trioxolane antimalarials with heme has been investigated to provide further insight into the mechanism of action for this important class of antimalarials. A series of trioxolanes with various antimalarial potencies was found to be unreactive in the presence of Fe(III) hemin, but all were rapidly degraded by reduced Fe(II) heme. The major reaction product from the heme-mediated degradation of biologically active trioxolanes was an alkylated heme adduct resulting from addition of a radical intermediate. Under standardized reaction conditions, a correlation (R 2 = 0.88) was found between the extent of heme alkylation and in vitro antimalarial activity, suggesting that heme alkylation may be related to the mechanism of action for these trioxolanes. Significantly less heme alkylation was observed for the clinically utilized artemisinin derivatives compared to the equipotent trioxolanes included in this study.
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Calic, Petar P. S., Mahta Mansouri, Peter J. Scammells i Sheena McGowan. "Driving antimalarial design through understanding of target mechanism". Biochemical Society Transactions 48, nr 5 (1.09.2020): 2067–78. http://dx.doi.org/10.1042/bst20200224.
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Malaria continues to be a global health threat, affecting approximately 219 million people in 2018 alone. The recurrent development of resistance to existing antimalarials means that the design of new drug candidates must be carefully considered. Understanding of drug target mechanism can dramatically accelerate early-stage target-based development of novel antimalarials and allows for structural modifications even during late-stage preclinical development. Here, we have provided an overview of three promising antimalarial molecular targets, PfDHFR, PfDHODH and PfA-M1, and their associated inhibitors which demonstrate how mechanism can inform drug design and be effectively utilised to generate compounds with potent inhibitory activity.
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Gomides, Ana, Gilda Ferreira, Adriana Kakehasi, Marcus Lacerda, Cláudia Marques, Licia Mota, Eduardo Paiva i in. "Impact of Chronic Use of Antimalarials on SARS-CoV-2 Infection in Patients With Immune-Mediated Rheumatic Diseases: Protocol for a Multicentric Observational Cohort Study". JMIR Research Protocols 9, nr 10 (14.10.2020): e23532. http://dx.doi.org/10.2196/23532.
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Background COVID-19, caused by the virus SARS-CoV-2, has brought extensive challenges to the scientific community in recent months. Several studies have been undertaken in an attempt to minimize the impact of the disease worldwide. Although new knowledge has been quickly disseminated, including viral mechanisms, pathophysiology, and clinical findings, there is a lack of information on the effective pharmacological management of this disease. In vitro studies have shown some benefits related to the use of antimalarials (chloroquine and hydroxychloroquine) for inhibiting SARS-CoV-2. However, the data from open clinical trials on COVID-19 patients are controversial. Objective We present the protocol for a research project that compares the potential protective effect of antimalarials in preventing moderate-to-severe forms of COVID-19 in two groups: (1) patients treated chronically with antimalarials for rheumatic diseases and (2) other members of the patients’ household who have not been diagnosed with rheumatic diseases and are not taking antimalarials. Methods This is a 24-week, prospective, observational cohort study comprising patients from public and private health services across Brazil, who chronically use antimalarials for the treatment of immune-mediated rheumatic diseases, osteoarthritis, or chikungunya-related arthropathy. A total of six sequential phone interviews were scheduled during the COVID-19 outbreak in five different regions of Brazil. Information regarding social, epidemiological, and demographic data, as well as details about rheumatic diseases, antimalarials, comorbidities, and concomitant medication, is being recorded using a specific online form in the REDCap database. Symptoms suggestive of COVID-19, including fever, cough, dyspnea, anosmia, and dysgeusia, are being self-reported and collected via phone interviews. Our main outcomes are hospitalization, need of intensive care unit, and death. Results Recruitment began at the end of March 2020, and the inclusion was done during an 8-week period (from March 29 to May 17) with a total of 10,443 individuals enrolled at baseline, 5166 of whom have rheumatic diseases, from 23 tertiary rheumatology centers across 97 Brazilian cities. Data analysis is scheduled to begin after all inclusion data have been collected. Conclusions This study, which includes a large sample of chronic antimalarial users, will allow us to explore whether SARS-CoV-2 infection may be associated with immune-mediated rheumatic diseases and long-term antimalarial usage. Trial Registration Brazilian Registry of Clinical Trials RBR–9KTWX6; http://www.ensaiosclinicos.gov.br/rg/RBR-9ktwx6/ International Registered Report Identifier (IRRID) DERR1-10.2196/23532
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&NA;. "Antimalarials". Reactions Weekly &NA;, nr 1363 (sierpień 2011): 7–8. http://dx.doi.org/10.2165/00128415-201113630-00024.
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&NA;. "Antimalarials". Reactions Weekly &NA;, nr 540 (marzec 1995): 5. http://dx.doi.org/10.2165/00128415-199505400-00008.
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&NA;. "Antimalarials". Drugs & Therapy Perspectives 9, nr 6 (marzec 1997): 13–16. http://dx.doi.org/10.2165/00042310-199709060-00005.
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Van Beek, Marta J., i Warren W. Piette. "Antimalarials". Dermatologic Therapy 14, nr 2 (czerwiec 2001): 143–53. http://dx.doi.org/10.1046/j.1529-8019.2001.014002143.x.
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Van Beek, Marta J., i Warren W. Piette. "ANTIMALARIALS". Dermatologic Clinics 19, nr 1 (styczeń 2001): 147–60. http://dx.doi.org/10.1016/s0733-8635(05)70236-9.
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Willoughby, Joanne S., i Neil H. Shear. "Antimalarials". Clinics in Dermatology 7, nr 3 (lipiec 1989): 60–68. http://dx.doi.org/10.1016/0738-081x(89)90008-4.
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SMITH, PAUL W., THIERRY T. DIAGANA i BRYAN K. S. YEUNG. "Progressing the global antimalarial portfolio: finding drugs which target multiple Plasmodium life stages". Parasitology 141, nr 1 (10.06.2013): 66–76. http://dx.doi.org/10.1017/s0031182013000747.
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SUMMARYThe number of novel antimalarial candidates entering preclinical development has seen an increase over the last several years. Most of these drug candidates were originally identified as hits coming from screening large chemical libraries specifically targeting the asexual blood stages of Plasmodium falciparum. Indeed, a large proportion of the current antimalarial arsenal has mainly targeted the asexual blood stage which is responsible for clinical symptoms of the disease. However, as part of the eradication agenda and to address resistance, any next-generation antimalarial should have additional activity on at least one other parasite life stage, i.e. gametocytocidal and/or tissue schizonticidal activity. We have applied this approach by screening compounds with intrinsic activity on asexual blood stages in assays against sexual and liver stages and identified two new antimalarial chemotypes with activity on multiple parasite life stages. This strategy can be expanded to identify other chemical classes of molecules with similar activity profiles for the next generation antimalarials. The following review summarizes the discovery of the spiroindolones and imidazolopiperazine classes of antimalarials developed by the NGBS consortium (Novartis Institute for Tropical Diseases, Genomic Institute of the Novartis Research Foundation, Biomedical Primate Research Center, and the Swiss Tropical and Public Health Institute) currently in clinical trials.
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Bhandari, Prasan R., i Apeksha Bhandary. "Variation of cost among anti-malarial drugs available in Indian market". International Journal of Basic & Clinical Pharmacology 8, nr 11 (22.10.2019): 2408. http://dx.doi.org/10.18203/2319-2003.ijbcp20194775.
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Background: There are numerous brands of antimalarial existent in the market. Expensive drugs could result in financial drain that causes reduced compliance or even non-compliance. Non-adherence to therapy could consequently cause partial treatment that leads to higher morbidity and in certain cases mortality too. Thus this evaluation was conducted to measure the cost disparity of malaria therapy.Methods: The maximum and minimum price of each brand of the drug in Indian rupee rate was noted by using the latest edition of current index of medical specialities. The cost ratio and the percentage cost variation for individual drug brands were calculated.Results: The analysis of data reflected a considerable cost variation among antimalarial drugs. Chloroquine DS 500 mg showed the highest cost ratio and cost variation (cost ratio=15.3 and % cost variation=1434). Overall injectable antimalarials showed considerable cost variation as compared to oral antimalarial agents.Conclusions: The maximum variation shown by oral antimalarial was found to be for chloroquine DS 500 tablet. But there was significant price variation among injectable antimalarial. Injectable antimalarials are often the choice of drug when dealing with critically ill malaria patients specially when suffering from complicated malaria. So, such significant price variation creates burden on poor patients economically which leads to non-compliance and hence increased morbidity and mortality due to incomplete treatment.
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Veiga, Maria Isabel, Nuno S. Osório, Pedro Eduardo Ferreira, Oscar Franzén, Sabina Dahlstrom, J. Koji Lum, Francois Nosten i José Pedro Gil. "Complex Polymorphisms in the Plasmodium falciparum Multidrug Resistance Protein 2 Gene and Its Contribution to Antimalarial Response". Antimicrobial Agents and Chemotherapy 58, nr 12 (29.09.2014): 7390–97. http://dx.doi.org/10.1128/aac.03337-14.
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ABSTRACTPlasmodium falciparumhas the capacity to escape the actions of essentially all antimalarial drugs. ATP-binding cassette (ABC) transporter proteins are known to cause multidrug resistance in a large range of organisms, including theApicomplexaparasites.P. falciparumgenome analysis has revealed two genes coding for the multidrug resistance protein (MRP) type of ABC transporters:Pfmrp1, previously associated with decreased parasite drug susceptibility, and the poorly studiedPfmrp2. The role ofPfmrp2polymorphisms in modulating sensitivity to antimalarial drugs has not been established. We herein report a comprehensive account of thePfmrp2genetic variability in 46 isolates from Thailand. A notably high frequency of 2.8 single nucleotide polymorphisms (SNPs)/kb was identified for this gene, including some novel SNPs. Additionally, we found thatPfmrp2harbors a significant number of microindels, some previously not reported. We also investigated the potential association of the identifiedPfmrp2polymorphisms with alteredin vitrosusceptibility to several antimalarials used in artemisinin-based combination therapy and with parasite clearance time. Association analysis suggestedPfmrp2polymorphisms modulate the parasite'sin vitroresponse to quinoline antimalarials, including chloroquine, piperaquine, and mefloquine, and association within vivoparasite clearance. In conclusion, our study reveals that thePfmrp2gene is the most diverse ABC transporter known inP. falciparumwith a potential role in antimalarial drug resistance.
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Taylor, Dennis K., Thomas D. Avery, Ben W. Greatrex, Edward R. T. Tiekink, Ian G. Macreadie, Peter I. Macreadie, Adam D. Humphries i in. "Novel Endoperoxide Antimalarials: Synthesis, Heme Binding, and Antimalarial Activity". Journal of Medicinal Chemistry 47, nr 7 (marzec 2004): 1833–39. http://dx.doi.org/10.1021/jm0305319.
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Warhurst, David C. "Antimalarial drugs II: Current antimalarials and new drug development". Trends in Pharmacological Sciences 6 (styczeń 1985): 302–4. http://dx.doi.org/10.1016/0165-6147(85)90140-3.
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Wright, Colin W. "Traditional antimalarials and the development of novel antimalarial drugs". Journal of Ethnopharmacology 100, nr 1-2 (sierpień 2005): 67–71. http://dx.doi.org/10.1016/j.jep.2005.05.012.
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Wilson, Danny W., Christine Langer, Christopher D. Goodman, Geoffrey I. McFadden i James G. Beeson. "Defining the Timing of Action of Antimalarial Drugs against Plasmodium falciparum". Antimicrobial Agents and Chemotherapy 57, nr 3 (14.01.2013): 1455–67. http://dx.doi.org/10.1128/aac.01881-12.
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ABSTRACTMost current antimalarials for treatment of clinicalPlasmodium falciparummalaria fall into two broad drug families and target the food vacuole of the trophozoite stage. No antimalarials have been shown to target the brief extracellular merozoite form of blood-stage malaria. We studied a panel of 12 drugs, 10 of which have been used extensively clinically, for their invasion, schizont rupture, and growth-inhibitory activity using high-throughput flow cytometry and new approaches for the study of merozoite invasion and early intraerythrocytic development. Not surprisingly, given reported mechanisms of action, none of the drugs inhibited merozoite invasionin vitro. Pretreatment of erythrocytes with drugs suggested that halofantrine, lumefantrine, piperaquine, amodiaquine, and mefloquine diffuse into and remain within the erythrocyte and inhibit downstream growth of parasites. Studying the inhibitory activity of the drugs on intraerythrocytic development, schizont rupture, and reinvasion enabled several different inhibitory phenotypes to be defined. All drugs inhibited parasite replication when added at ring stages, but only artesunate, artemisinin, cycloheximide, and trichostatin A appeared to have substantial activity against ring stages, whereas the other drugs acted later during intraerythrocytic development. When drugs were added to late schizonts, only artemisinin, cycloheximide, and trichostatin A were able to inhibit rupture and subsequent replication. Flow cytometry proved valuable forin vitroassays of antimalarial activity, with the free merozoite population acting as a clear marker for parasite growth inhibition. These studies have important implications for further understanding the mechanisms of action of antimalarials, studying and evaluating drug resistance, and developing new antimalarials.
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McCarthy, Peter J., Bracken F. Roberts, Abigail Carbonell, Jill Roberts, Amy E. Wright i Debopam Chakrabarti. "Marine Microbiome as a Source of Antimalarials". Tropical Medicine and Infectious Disease 4, nr 3 (13.07.2019): 103. http://dx.doi.org/10.3390/tropicalmed4030103.
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It is important to discover novel antimalarial pharmacophores because of the widespread emergence of Plasmodium falciparum isolates resistant to the available drugs. Secondary metabolites derived from microbes associated with marine invertebrates are a valuable resource for the discovery of novel drug leads. However, the potential of marine microbes as a source of antimalarials has not been explored. We investigated the promise of marine microorganisms for the production of antimalarial activities by testing 2365 diverse microbial extracts using phenotypic screening of a multidrug resistant chloroquine resistant P. falciparum strain. We conducted counter screening against mammalian cells for the 317 active extracts that exhibited more than 70% inhibition at 1 µg/mL. The screen identified 17 potent bioactive leads from a broad range of taxa. Our results establish that the marine microbiome is a rich source of antiplasmodial compounds that warrants in depth exploration.
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Rizki, Andita Fitri Mutiara, Wihda Aisarul Azmi, Muhaimin Muhaimin, Melva Louisa, I. Made Artika i Josephine Elizabeth Siregar. "Antimalarial Activity of Mangrove Plants and Possible Mechanisms of Action: A Scoping Review". Molekul 19, nr 1 (14.03.2024): 98. http://dx.doi.org/10.20884/1.jm.2024.19.1.9236.
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Malaria is one of life threatening-infectious diseases with high mortality rate in African regions. Malaria is also one of public health problem in most of Southeast Asia (SEA) regions. This disease is caused by a Apicomplexan parasite; Plasmodium sp., which can be transmitted from humans to humans via Anopheles sp. To date, the need of a new antimalarial drug is still high, due to the rapid increase of drug resistance. Natural-derived drug candidates are still being used by researchers to develop new antimalarials. One of the natural resources which could potentially be a source of antimalarial agents are mangrove plants. Traditionally, mangrove plants have been employed as antibacterial, antioxidant, anticancer, and antidiabetic. Therefore, we conducted a scoping review to identify, evaluate and summarize findings of newly found antimalarial drug activity from mangrove plants and elaborate the possible mechanism of actions in killing the parasites. From several databases, we found six mangrove species which have been suggested as potential antimalarial sources. Various phytochemical compounds in extracts made from those plants were revealed to exert antimalarial activity. These include alkaloids, flavonoids, tannins, phenols, terpenoids, saponins, coumarins, triterpenes, glycosides, and anthraquinones which were indicated to have antimalarial activity against Plasmodium. From eight studies investigating mangrove plant extracts, no toxic effects were shown. Therefore, considering the available evidences, we suggested that mangrove plants can be used as a source for the discovery of antimalarial compounds with promising activities against Plasmodium sp. However, deeper understanding on the exact mechanisms of their actions still requires further elucidation.
Keywords: Antimalaria, Anthraquinone, Mangrove, Plasmodium sp., Protozoa
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Marciniak, Stephanie. "Counterfeit Antimalarials and the Commodification of Health". NEXUS: The Canadian Student Journal of Anthropology 22 (11.11.2014): 5–18. http://dx.doi.org/10.15173/nexus.v22i1.12.
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Counterfeit and substandard medicines are a persistent threat to the global control and eradication of infectious diseases. The issue is particularly acute in developing countries due to the lack of local and international pharmaceutical surveillance networks that ultimately enables this industry to thrive . In this context, the inability to fulfill the fundamental right of individuals to access life-saving essential medicines is a critical public health challenge. Accordingly, this paper analyzes the crisis of counterfeit and substandard antimalarials in sub-Saharan Africa through a multidimensional framework. Of primary importance is the vulnerability of healthcare systems to market-driven forces which facilitates the emergence and sustainability of barriers in the access to high-quality antimalarials. Consequently, the proliferation of the informal drug market is contextualized by the dire need for affordable malaria treatment and cultural perceptions of the quality of care from formal sectors (e.g., clinics, hospitals). The impact of counterfeit antimalarials cannot be understated, ranging from increased morbidity, such as adverse effects from substandard product ingredients, to heightening the resistance of populations to the final line of antimalarial treatment (artemisinin-combination therapy). The ability of international humanitarian organizations and various levels of government to combat the issue of counterfeit medicines remains a daunting task, as the right to health has become a commodity.
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Olafson, Katy N., Megan A. Ketchum, Jeffrey D. Rimer i Peter G. Vekilov. "Mechanisms of hematin crystallization and inhibition by the antimalarial drug chloroquine". Proceedings of the National Academy of Sciences 112, nr 16 (23.03.2015): 4946–51. http://dx.doi.org/10.1073/pnas.1501023112.
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Hematin crystallization is the primary mechanism of heme detoxification in malaria parasites and the target of the quinoline class of antimalarials. Despite numerous studies of malaria pathophysiology, fundamental questions regarding hematin growth and inhibition remain. Among them are the identity of the crystallization medium in vivo, aqueous or organic; the mechanism of crystallization, classical or nonclassical; and whether quinoline antimalarials inhibit crystallization by sequestering hematin in the solution, or by blocking surface sites crucial for growth. Here we use time-resolved in situ atomic force microscopy (AFM) and show that the lipid subphase in the parasite may be a preferred growth medium. We provide, to our knowledge, the first evidence of the molecular mechanisms of hematin crystallization and inhibition by chloroquine, a common quinoline antimalarial drug. AFM observations demonstrate that crystallization strictly follows a classical mechanism wherein new crystal layers are generated by 2D nucleation and grow by the attachment of solute molecules. We identify four classes of surface sites available for binding of potential drugs and propose respective mechanisms of drug action. Further studies reveal that chloroquine inhibits hematin crystallization by binding to molecularly flat {100} surfaces. A 2-μM concentration of chloroquine fully arrests layer generation and step advancement, which is ∼104× less than hematin’s physiological concentration. Our results suggest that adsorption at specific growth sites may be a general mode of hemozoin growth inhibition for the quinoline antimalarials. Because the atomic structures of the identified sites are known, this insight could advance the future design and/or optimization of new antimalarials.
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MWANGI, JONATHAN M., i LISA C. RANFORD-CARTWRIGHT. "Genetic and genomic approaches for the discovery of parasite genes involved in antimalarial drug resistance". Parasitology 140, nr 12 (9.08.2013): 1455–67. http://dx.doi.org/10.1017/s0031182013000954.
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SUMMARYThe biggest threat to the war on malaria is the continued evolution of drug resistance by the parasite. Resistance to almost all currently available antimalarials now exists inPlasmodium falciparumwhich causes the most suffering among all human malaria parasites. Monitoring of antimalarial efficacy and the development and subsequent spread of resistance has become an important part in the treatment and control of malaria. With recent reports of reduced efficacy of artemisinin, the current recommended treatment for uncomplicated malaria, there is urgent need for better methods to recognize and monitor drug resistance for effective treatment. Molecular markers have become a welcome addition to complement the more laborious and costlyin vitroandin vivomethods that have traditionally been used to monitor drug resistance. However, there are currently no molecular markers for resistance to some antimalarials. This review highlights the role of the various genetic and genomic approaches that have been used in identifying the molecular markers that underlie drug resistance inP. falciparum. These approaches include; candidate genes, genetic linkage and genome-wide association studies. We discuss the requirements and limitations of each approach and use various examples to illustrate their contributions in identifying genomic regions of the parasite associated with antimalarial drug responses.
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Brito, Daniel, Edgar Marquez, Felix Rosas i Ennis Rosas. "Predicting new potential antimalarial compounds by using Zagreb topological indices". AIP Advances 12, nr 4 (1.04.2022): 045017. http://dx.doi.org/10.1063/5.0089325.
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Molecular topology allows describing molecular structures following a two-dimensional approach by taking into account how the atoms are arranged internally through a connection matrix between the atoms that are part of a structure. Various molecular indices (unique for each molecule) can be determined, such as Zagreb, Balaban, and topological indices. These indices have been correlated with physical chemistry properties such as molecular weight, boiling point, and electron density. Furthermore, their relationship with a specific biological activity has been found in other reports. Therefore, its knowledge and interpretation could be critical in the rational design of new compounds, saving time and money in their development process. In this research, the molecular graph of antimalarials already in the pharmaceutical market, such as chloroquine, primaquine, quinine, and artemisinin, was calculated and used to compute the Zagreb indices; a relationship between these indices and the antimalarial activities was found. According to the results reported in this work, the smaller the Zagreb indices, the higher the antimalarial activity. This relationship works very well for other compounds series. Therefore, it seems to be a fundamental structural requirement for this activity. Three triazole-modified structures are proposed as possible potential antimalarials based on this hypothesis. Finally, this work shows that the Zagreb indices could be a cornerstone in designing and synthesizing new antimalarial compounds, albeit they must be proved experimentally.
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Boulet, Coralie, Ghizal Siddiqui, Taylah L. Gaynor, Christian Doerig, Darren J. Creek i Teresa G. Carvalho. "Red Blood Cell BCL-xL Is Required for Plasmodium falciparum Survival: Insights into Host-Directed Malaria Therapies". Microorganisms 10, nr 4 (15.04.2022): 824. http://dx.doi.org/10.3390/microorganisms10040824.
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The development of antimalarial drug resistance is an ongoing problem threatening progress towards the elimination of malaria, and antimalarial treatments are urgently needed for drug-resistant malaria infections. Host-directed therapies (HDT) represent an attractive strategy for the development of new antimalarials with untapped targets and low propensity for resistance. In addition, drug repurposing in the context of HDT can lead to a substantial decrease in the time and resources required to develop novel antimalarials. Host BCL-xL is a target in anti-cancer therapy and is essential for the development of numerous intracellular pathogens. We hypothesised that red blood cell (RBC) BCL-xL is essential for Plasmodium development and tested this hypothesis using six BCL-xL inhibitors, including one FDA-approved compound. All BCL-xL inhibitors tested impaired proliferation of Plasmodium falciparum 3D7 parasites in vitro at low micromolar or sub-micromolar concentrations. Western blot analysis of infected cell fractions and immunofluorescence microscopy assays revealed that host BCL-xL is relocated from the RBC cytoplasm to the vicinity of the parasite upon infection. Further, immunoprecipitation of BCL-xL coupled with mass spectrometry analysis identified that BCL-xL forms unique molecular complexes with human μ-calpain in uninfected RBCs, and with human SHOC2 in infected RBCs. These results provide interesting perspectives for the development of host-directed antimalarial therapies and drug repurposing efforts.
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Maima, Ausitine Juma. "Evaluation of Counterfeit Antimalarial Drug Awareness and Knowledge Among Pharmacy Attendants in Nairobi County, Kenya". African Journal of Pharmacy and Alternative Medicine 2, nr 1 (9.04.2024): 21–31. http://dx.doi.org/10.58460/ajpam.v2i1.84.
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Malaria presents a significant health challenge in sub-Saharan Africa, leading to an increased demand for antimalarial drugs. However, the global prevalence of counterfeit drugs, estimated at 10%, jeopardizes treatment efficacy, resulting in an annual economic loss of $75 billion. In Kenya, the accessibility of antimalarials, particularly through pharmacies, exacerbates this issue. This study sought to address knowledge gaps on counterfeit antimalarials among pharmacy attendants in Nairobi County. Utilizing a cross-sectional descriptive survey, the research evaluated awareness levels of counterfeit antimalarial drugs among pharmacy attendants. The study involved five subsections, focusing on pharmacy professionals engaged in antimalarial sales, with a sample size of 251 determined using Cochran’s formula. Data collection methods included questionnaires and observation checklists. Instrument validity was ensured through a pre-test analysis, and reliability was assessed via training and a test-retest approach. Data analysis, performed using Microsoft Excel and SPSS, incorporates ANOVA at a 95% significance level. Surveying 251 pharmacy attendants in Nairobi revealed a slightly higher distribution of males (52.2%) than females (47.8%), primarily aged 18-24 (51%), holding TVET qualifications (60.2%), with an average work experience of four years (30.7%). Community pharmacies dominated (61.8%), and pharmaceutical technologists constituted the most prevalent professionals (29.5%). Artemether-Lumefantrine is the preferred antimalarial (36.7%). Concerning awareness of counterfeit drugs, 39.8% rely on the Pharmacy and Poisons Board, with 72.9% knowledgeable about counterfeit antimalarial effects. The study identifies correlations between knowledge levels and the color and odor of antimalarial drugs. The regression model (R²=0.093, F (3, 247) =8.422, p<0.001) signifies the predictive efficacy of drug characteristics on knowledge, with color and odor emerging as robust predictors. Despite commendable knowledge, there exists a perception gap among pharmacy attendants regarding counterfeit antimalarial drug campaigns and awareness training. Addressing this gap is crucial to preventing an increased distribution of counterfeit drugs in the sector.