Journal articles on the topic 'Malaria – Drug therapy'
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Kondrashin, A. V., E. V. Stepanova, L. F. Morozova, V. P. Sergiev, M. S. Maksimova, N. A. Turbabina, N. S. Malysheva, et al. "Artemether and imatinib combination therapy against malaria infection." Infekcionnye bolezni 19, no. 1 (2021): 139–43. http://dx.doi.org/10.20953/1729-9225-2021-1-139-143.
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Artemisinin-based combination therapy (ACT) is recommended by the World Health Organization (WHO) as the first and second line of treatment for uncomplicated malaria caused by P. falciparum, as well as for chloroquine-resistant P. vivax malaria. Despite the large number of antimalarial drugs, there is no any ideal drug, since each individual combination of drugs or monotherapy have their own limitations, ranging from their triple (activity) in relation to certain forms of the development of Plasmodium in the human body, side effects, toxicity and resistance. During the course of the study carried out, the most promising compound-candidate was selected – imatinib, which is currently used as targeted therapy for a number of oncological diseases. The objective of this work is to evaluate the efficacy of the combined use of imatinib and artemether in vivo studies on the human malarial model – the rodent malaria parasites Plasmodium berghei. Dut to the optimally selected treatment scheme, it was possible to reduce the dosage of imatinib twice – to 0,25 mg/kg, and that of artemether three times – to 33 mg/kg. The use of this scheme made it possible to considerably reduce the toxic effect of these drugs due to the potentiation of antimalarial effect. Key words: malaria, drug resistance, telomerase inhibitors, imatinib, chemotherapy of malaria
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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.
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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
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Kulkarni, A. V., L. Kasturi, A. Amin, and V. Mashankar. "Therapy and drug resistance in malaria." Indian Journal of Pediatrics 67, no. 1 (January 2000): 33–35. http://dx.doi.org/10.1007/bf02802634.
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Alven, Sibusiso, and Blessing Aderibigbe. "Combination Therapy Strategies for the Treatment of Malaria." Molecules 24, no. 19 (October 7, 2019): 3601. http://dx.doi.org/10.3390/molecules24193601.
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Malaria is a vector- and blood-borne infection that is responsible for a large number of deaths around the world. Most of the currently used antimalarial therapeutics suffer from drug resistance. The other limitations associated with the currently used antimalarial drugs are poor drug bioavailability, drug toxicity, and poor water solubility. Combination therapy is one of the best approaches that is currently used to treat malaria, whereby two or more therapeutic agents are combined. Different combination therapy strategies are used to overcome the aforementioned limitations. This review article reports two strategies of combination therapy; the incorporation of two or more antimalarials into polymer-based carriers and hybrid compounds designed by hybridization of two antimalarial pharmacophores.
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Trasia, Reqgi First. "Use of Combination Therapy in Malaria Treatment and Prevention in Indonesia." Journal of Pharmaceutical and Sciences 4, no. 1 (June 30, 2021): 29–33. http://dx.doi.org/10.36490/journal-jps.com.v4i1.61.
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Malaria is still a health problem in Indonesia. Treatment of malaria often encounters obstacles. Resistance to various malaria drugs in some areas causes an increase in morbidity and mortality due to malaria. Rational use of malaria drugs that are still effective and available is important. Therefore, this article will review the use of combination therapy in the treatment of malaria in Indonesia. The purpose of using combination therapy is to increase the efficacy of treatment and slow down the occurrence of resistance to each component in the drug. From this article, it can be concluded that artemisinin-based combinations using artemisinin derivatives are still effective for use as combination therapy against malaria. This combination can be a fixed combination or co-administered. The drugs that can be combined are 4-aminoquinoline, antifolate, 4-quinoline-methanol, artemisinin and its derivatives, antibiotics, and atovaquone-proguanil. It is hoped that the combination of these drugs can still be used for a long period of time, remain safe, effective and affordable by the community.
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Dijanic, Christopher, Jillian Nickerson, Sunita Shakya, Amanda Dijanic, and Marilyn Fabbri. "Relapsing Malaria: A Case Report of Primaquine Resistance." Case Reports in Infectious Diseases 2018 (2018): 1–3. http://dx.doi.org/10.1155/2018/9720823.
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Primaquine (an 8-aminoquinoline malarial therapy) is the only FDA-approved therapy to treat the hypnozoite stage of P. vivax. We think of relapse occurring because of parasitic resistance or poor compliance secondary to drug toxicities. However, in patients with repeated treatment failure, we must consider CYP-450 mutations affecting drug metabolism as an important cause of relapse. A 47-year-old man who travelled to a jungle in Venezuela was diagnosed with P. falciparum and P. vivax in July 2015. He was treated with seven rounds of primaquine-based therapy in the following year, all resulted in relapse without further exposure to endemic areas. On his eighth presentation, he was found to have CYP-4502D6 mutation that affected the metabolism and activation of primaquine. Thereafter, he was treated without relapse. Primaquine efficacy depends on many factors. Understanding the mechanism responsible for malaria relapse is paramount for successful treatment and reduction in morbidity and mortality. This case illustrates the importance of considering cytochrome mutations that affect drug efficacy in cases of relapsing malaria.
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Kain, Kevin C. "Chemotherapy of Drug-Resistant Malaria." Canadian Journal of Infectious Diseases 7, no. 1 (1996): 25–33. http://dx.doi.org/10.1155/1996/139612.
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OBJECTIVE: To review the impact of drug-resistant malaria on current management of plasmodial infections.DATA SOURCES: A MEDLINE search of the English-language medical literature from 1985 to 1995; bibliographies of selected papers; international malaria advisory experts.DATA SYNTHESIS: Combinations of artemisinin derivatives and mefloquine or atovaquone plus proguanil appear to be the most active drug regimens against multidrug-resistant falciparum malaria from Southeast Asia. The optimal therapy for chloroquine-resistantPlasmodium vivaxis unknown, but recent data indicate that halofantrine or chloroquine plus high doses of primaquine are efficacious.CONCLUSIONS: The incidence of drug-resistant malaria continues to increase at a rate that exceeds new drug development. Ultimately the control of malaria will require more creative approaches than just the development of additional inhibitory drugs. These might include the identification of biochemical pathways unique to the parasite (such as drug efflux and heme polymerization), making it possible to design new classes of antimalarial agents that are selectively toxic to the parasite; methods to block parasite development in the mosquito vector; and multistage vaccines against asexual and sexual stages to block both the pathophysiology and the transmission of disease.
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Orwa, Titus Okello, Rachel Waema Mbogo, and Livingstone Serwadda Luboobi. "Multiple-Strain Malaria Infection and Its Impacts on Plasmodium falciparum Resistance to Antimalarial Therapy: A Mathematical Modelling Perspective." Computational and Mathematical Methods in Medicine 2019 (June 11, 2019): 1–26. http://dx.doi.org/10.1155/2019/9783986.
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The emergence of parasite resistance to antimalarial drugs has contributed significantly to global human mortality and morbidity due to malaria infection. The impacts of multiple-strain malarial parasite infection have further generated a lot of scientific interest. In this paper, we demonstrate, using the epidemiological model, the effects of parasite resistance and competition between the strains on the dynamics and control of Plasmodium falciparum malaria. The analysed model has a trivial equilibrium point which is locally asymptotically stable when the parasite’s effective reproduction number is less than unity. Using contour plots, we observed that the efficacy of antimalarial drugs used, the rate of development of resistance, and the rate of infection by merozoites are the most important parameters in the multiple-strain P. falciparum infection and control model. Although the drug-resistant strain is shown to be less fit, the presence of both strains in the human host has a huge impact on the cost and success of antimalarial treatment. To reduce the emergence of resistant strains, it is vital that only effective antimalarial drugs are administered to patients in hospitals, especially in malaria-endemic regions. Our results emphasize the call for regular and strict surveillance on the use and distribution of antimalarial drugs in health facilities in malaria-endemic countries.
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Spencer, Lilian M., Andreyna Peña-Quintero, Nieves Canudas, Inexis Bujosa, and Neudo Urdaneta. "Antimalarial effect of two photo-excitable compounds in a murine model with Plasmodium berghei (Haemosporida: Plasmodiidae)." Revista de Biología Tropical 66, no. 2 (May 24, 2018): 880. http://dx.doi.org/10.15517/rbt.v66i2.33420.
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Malaria represents a major health problem worldwide, affecting around 198 million people in 2016 according to WHO database. For decades, anti-malarial drug therapy has been used in the battle against this disease and its uncontrolled usage in endemic areas has developed the appearance of the drug resistance. Thus, it has emerged the necessity of finding new treatments that could be used as an alternative cure to malaria infection. The aim of this work was the evaluation of two photo-excitable compounds: Compound 1, which is (2E)-3-(4-dimethylamino-phenyl)-1-(4-imidazol-1-yl-phenyl)prop-2-en-1-one) and Compound 2, (1E,4E)-1-[4-(dimethylamino)phenyl]-5-(4-methoxyphenyl)-1,4-pentadiene-3-one) as possible anti-malaria drugs with Plasmodium berghei ANKA strain in BALB/c mice as murine model. Cytotoxicity effect was evaluated by a cell proliferation by colorimetry assay (MTS); and the drug incorporation into the parasite was assessed in vitro with Indirect Immunofluorescence Assay (IFA) to determine the localization of the drugs into the parasitized red blood cells (RBCs). Finally, the curative effect of compounds no-radiation (fundamental state) and ration drugs were evaluated by oral drug administration of this drugs in BALB/c mice and chloroquine was used as positive control. This curative effect was determined daily by the parasitemia percentage. The results showed that both compounds were cytotoxic in fundamental state. Furthermore, cytotoxic effect was increased after radiation into the Solar Simulator, and compound 2 was more cytotoxic than compound 1. Curative assays showed that both compounds in fundamental state were non effective as anti-malarial drug. However, in the curative assays in the mice treated with compound 2, when this was ration showed a survival rate of 33 % and a parasitemia percentage decrease in compare to compound 1. Although the compounds did not show a similar or better anti-malarial effect than Chloroquine, Compound 2 presented certain anti-malarial effect after solar radiation. Rev. Biol. Trop. 66(2): 880-891. Epub 2018 June 01.
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Chahar, Madhvi, Anup Anvikar, and Neena Valecha. "Development and Evaluation of a Novel HNB Based Isothermal Amplification Assay for Fast Detection of Pyrimethamine Resistance (S108N) in Plasmodium falciparum." International Journal of Environmental Research and Public Health 16, no. 9 (May 10, 2019): 1635. http://dx.doi.org/10.3390/ijerph16091635.
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Sulphadoxine and pyrimethamine (SP) have been used as long-acting partner antimalarial drugs in artemisinin combination therapy (ACT) for falciparum malaria. The emergence and increasing spread of SP resistance in malaria-endemic areas have become a challenge for the control of malaria. Therefore, regular monitoring of the mutation status of partner drugs is important for the better management of drug policy. There are limitations with traditional molecular methods and there is an urgent need for an easy method for diagnosis of drug resistance. In this study we have introduced and developed a novel single nucleotide polymorphism loop-mediated isothermal amplification (SNP–LAMP) approach based on a hydroxynaphthol blue (HNB) indicator for the easier and quicker detection of pyrimethamine resistance in Plasmodium falciparum malaria. To implement this novel approach, many sets of LAMP primers were designed and tested. Finally, one set of forward inner primer M1 (FIPM1) of LAMP primer was selected that specifically distinguishes pyrimethamine-resistant P. falciparum malaria. The LAMP reactions were optimized at 60–66 °C for 45 min. High sensitivity (7 parasites/µL) was observed with 10−4 fold dilutions (<2 ng DNA) of genomic DNA. Moreover, this approach has the potential to be applied even in laboratories unfamiliar with PCR or other molecular methods, and in future, this can be helpful for the better management of anti-malarial policy.
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Chiyaka, C., W. Garira, and S. Dube. "Modelling Immune Response and Drug Therapy in Human Malaria Infection." Computational and Mathematical Methods in Medicine 9, no. 2 (2008): 143–63. http://dx.doi.org/10.1080/17486700701865661.
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A new intra-host model of malaria that describes the dynamics of the blood stages of the parasite and its interaction with red blood cells and immune effectors is proposed. Local and global stability of the disease free equilibrium are investigated. Conditions for existence and uniqueness of the endemic equilibrium are derived. An intra-host basic reproductive number is identified. We deduce that drugs based on inhibiting parasite production are more effective than those based on inhibiting merozoite invasion of erythrocytes. We extend the model to incorporate, in addition to immune response, drug therapy, following treatment with antimalarial drugs. Using stability analysis of the model, it is shown that infection can be eradicated within the host if the drug efficacy level exceeds a certain threshold value. It will persist if the efficacy is below this threshold. Numerical simulations are done to verify the analytic results and illustrate possible behaviour of the models.
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Sunitha G N, Satyavati Dulipala D, and Girish Gudi. "Effect of ritonavir on pharmacokinetics of antimalarial drug combinations in rats." International Journal of Research in Pharmaceutical Sciences 10, no. 3 (September 21, 2019): 2477–86. http://dx.doi.org/10.26452/ijrps.v10i3.1497.
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The current treatment for Human Immunodeficiency Virus (HIV) patients coinfected with malaria involves the coadministration of antimalarial and antiretroviral (ARV) drugs. The World Health Organization (WHO) recommends artemisinin-based therapy for malaria that usually consists of artemether, artesunate or dihydroartemisinin with non-artemisinin derivatives such as amodiaquine, lumefantrine and mefloquine. Protease inhibitors (PI) such as ritonavir contribute to the improved health of HIV-positive individuals, and the inclusion of ritonavir in antiretroviral regimens is common in clinical practice. Ritonavir is a potent inhibitor of human CYP3A4, which is the primary enzyme involved in the metabolism of many of artemisinin-based drugs, as well as amodiaquine and proguanil. Upon co-administration, ritonavir can potentially influence the metabolism and thus increase the systemic exposure of these drugs. In order to understand this pharmacokinetic (PK) drug interaction, the current work evaluated the effect of ritonavir (50 mg/kg orally) on the PK of antimalarial drug combinations in Sprague Dawley (SD) rats. When co-administered with ritonavir, the exposure (AUC) of the antimalarial drugs artemether, artesunate and proguanil was increased by approximately 3.5-fold. Correspondingly, peak plasma concentrations (Cmax) of these drugs increased as well. There was no apparent influence of ritonavir on the PK of lumefantrine, amodiaquine and atovaquone. This study demonstrates the potential influence of ritonavir on the pharmacokinetics of at least some anti-malarial drugs, likely a result of inhibition of CYP3A. Further evaluation of clinically relevant drug interaction in humans may be warranted to ensure safe and effective use of anti-malarial and anti-HIV drugs concomitantly.
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Kumari, Jyoti, Raj Kumar Sah, Nazar Mohamed Mohaideen. S, Shakeel Ahmad, Soumya Pati, and Shailja Singh. "Studying the Rationale of Fire Ant Sting Therapy Usage by the Tribal Natives of Bastar Revealed Ant Venom-Derived Peptides with Promising Anti-Malarial Activity." Toxins 14, no. 11 (November 11, 2022): 789. http://dx.doi.org/10.3390/toxins14110789.
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Prevailing drug resistance in malaria imposes the major roadblock for the existing interventions necessitating the timely need to search for alternative therapies. Ants in Solenopsis spp, termed ’Fire ants’, are well known for their aggressive behavior, which leads to the release of toxic venom. Notably, the tribal natives of the malaria-laden densely forested Bastar region, Chhattisgarh, India, use fire ant sting-based therapy to cure malaria-like high fever. Inspired by this, we have collected the fire ants from the forest of Bastar and extracted peptide and alkaloid fractions from ant venom using HPLC and analyzed them by LC/MS-based applications. Evaluation of the anti-malarial efficacy of these peptide fractions demonstrated a significant reduction in the growth of Plasmodium falciparum (Pf 3D7) in vitro, whereas the alkaloid fraction showed a negligible effect. in vitro hemolytic activity confirmed the venom peptide fraction to be non-hemolytic. Additionally, the venom peptide fraction is purely non-toxic to HepG2 cells. Anti-malarial efficiency of the same in Plasmodium berghei ANKA infected mice models showed a drastic reduction in parasitemia representing promising anti-malarial activity. Overall, our study has unraveled the scientific rationale underlying fire ant sting therapy used as a tribal naturotherapy for curing malaria-like fever, thus, introducing a way forward to develop nature-inspired anti-malarial chemotherapeutics.
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Winstanley, Peter, Stephen Ward, Robert Snow, and Alasdair Breckenridge. "Therapy of Falciparum Malaria in Sub-Saharan Africa: from Molecule to Policy." Clinical Microbiology Reviews 17, no. 3 (July 2004): 612–37. http://dx.doi.org/10.1128/cmr.17.3.612-637.2004.
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SUMMARY The burden of falciparum malaria remains as great as ever, and, as has probably always been the case, it is carried mainly by tropical Africa. Of the various means available for the control of malaria, the use of effective drugs remains the most important and is likely to remain so for a considerable time to come. Unfortunately, the extensive development of resistance by the parasite threatens the utility of most of the affordable classes of drug: the development of novel antimalarials has never been more urgently needed. Any attempt to understand the vast complexities of falciparum malaria in Africa requires an ability to think “from molecule to policy.” In consequence, the review ambitiously tries to examine the current pharmacopeia, the process by which new drugs are developed and the ways in which drugs are actually used, in both the formal and informal health sectors. The informal sector is particularly important in Africa, where around half of all antimalarial treatments are bought from informal outlets and taken at home without supervision by health care professionals: the potential impact of adherence on clinical outcome is discussed. Given that the full costs are carried by the patient in a large proportion of cases, the importance of drug affordability is explored. The review also discusses the splicing of new drugs into national policy. The various parameters that feed into deliberations on changes in drug policy are discussed.
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Daboer, JC, TO Afolaranmi, ME Banwat, YO Tagurum, and JD Gokir. "Malaria Diagnosis and Treatment Practices in Public Primary Health Care Clinics in Pankshin Local Government Area, Plateau State, Nigeria." Journal of Epidemiological Society of Nigeria 1 (February 28, 2017): 45–52. http://dx.doi.org/10.46912/jeson.14.
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Background: Malaria remains the most important infectious disease in sub-Saharan Africa. Over exposure of the parasite to antimalarial medicines has precipitated the emergence of drug resistance to these medicines. The World Health Organization in 2010 issued a new policy of universal parasite-based diagnosis as a prerequisite for treatment. This study aimed at determining if Primary Health Care workers in Pankshin Local Government Area are complying with the new policy.
Methods: Using stratified sampling technique, six clinics were selected from Pankshin Local Government Area. Relevant information on all patients treated for malaria between 1st May 2015 and 30th April 2016 was extracted from clinic records. All health workers who attended to patients were interviewed while a facility inventory form was used to collect information on availability of drugs and supplies. Data generated were analyzed using Statistical Package for Social Sciences version 20.
Results: Out of 2909 patients studied, only 37.3% were tested for malaria parasites before treatment; 68.4% of whom had microscopy while 20.5% had Rapid Diagnostic Test. For those not tested 22.5% had Artemisinin Combination Therapy while 48.1% had non-Artemisinin Combination Therapy. Out of those who tested negative for malaria parasite, 8.8% and 21.6% were treated with Artemisinin Combination Therapy and non-Artemisinin Combination Therapy respectively Those who tested positive received Artemisinin Combination Therapy alone (35.5%) or in combination with other drugs (64.5%). Testing influenced the choice of drug for malaria treatment and this was statistically significant (p < 0.001).
Conclusion: Pretreatment testing for malaria and adherence to test results in Primary Health Care clinics in Pankshin are low. Concerted efforts are required for their training and supervision on the current guidelines on malaria diagnosis and treatment.
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Serghides, Lena. "The Case for the Use of PPARγ Agonists as an Adjunctive Therapy for Cerebral Malaria." PPAR Research 2012 (2012): 1–12. http://dx.doi.org/10.1155/2012/513865.
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Cerebral malaria is a severe complication ofPlasmodium falciparuminfection associated with high mortality even when highly effective antiparasitic therapy is used. Adjunctive therapies that modify the pathophysiological processes caused by malaria are a possible way to improve outcome. This review focuses on the utility of PPARγ agonists as an adjunctive therapy for the treatment of cerebral malaria. The current knowledge of PPARγ agonist use in malaria is summarized. Findings from experimental CNS injury and disease models that demonstrate the potential for PPARγ agonists as an adjunctive therapy for cerebral malaria are also discussed.
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Siagian, Forman E., Ronny ., Apriani I. Sirra, Urip Susiantoro, and Melsipa Siregar. "Malaria related myalgia-arthralgia: an imported case report treated with anti-malarial drug." International Journal of Basic & Clinical Pharmacology 9, no. 10 (September 22, 2020): 1603. http://dx.doi.org/10.18203/2319-2003.ijbcp20203964.
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Malaria is still a major health problem in Indonesia, especially in endemic areas. We present an imported case of malaria with prominent subjective complaint of the patient is in the form of persistent muscles and joints pain. A 21 years old female with complaint of intermittent fever and persistent muscle joints paint since one week before seeing a doctor. She had history of repetitive attack of malaria tropica. Physical examination in general showed no clear derangements, but on thick and thin blood smear stained with Giemsa revealed malaria falciparum (+). Combo therapy of antimalarial drug soon be given and the patient healed with the disappearance of all previous complaint. Myalgia and arthralgia in case of malaria falciparum (+) might be the earliest subjective sign of rhabdomyolisis, a potentially fatal and lethal complication of malaria.
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SUTHERLAND, COLIN J., HAMZA BABIKER, MARGARET J. MACKINNON, LISA RANFORD-CARTWRIGHT, and BADRIA BABIKER EL SAYED. "Rational deployment of antimalarial drugs in Africa: should first-line combination drugs be reserved for paediatric malaria cases?" Parasitology 138, no. 12 (August 3, 2011): 1459–68. http://dx.doi.org/10.1017/s0031182011001144.
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SUMMARYArtemisinin-based combination therapy is exerting novel selective pressure upon populations of Plasmodium falciparum across Africa. Levels of resistance to non-artemisinin partner drugs differ among parasite populations, and so the artemisinins are not uniformly protected from developing resistance, already present in South East Asia. Here, we consider strategies for prolonging the period of high level efficacy of combination therapy for two particular endemicities common in Africa. Under high intensity transmission, two alternating first-line combinations, ideally with antagonistic selective effects on the parasite genome, are advocated for paediatric malaria cases. This leaves second-line and other therapies for adult cases, and for intermittent preventive therapy. The drug portfolio would be selected to protect the ‘premier’ combination regimen from selection for resistance, while maximising impact on severe disease and mortality in children. In endemic areas subject to low, seasonal transmission of Plasmodium falciparum, such a strategy may deliver little benefit, as children represent a minority of cases. Nevertheless, the deployment of other drug-based interventions in low transmission and highly seasonal areas, such as mass drug administration aimed to interrupt malaria transmission, or intermittent preventive therapy, does provide an opportunity to diversify drug pressure. We thus propose an integrated approach to drug deployment, which minimises direct selective pressure on parasite populations from any one drug component. This approach is suitable for qualitatively and quantitatively different burdens of malaria, and should be supported by a programme of routine surveillance for emerging resistance.
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Okoro, Roland Nnaemeka, and Muslim Olakunle Jamiu. "The Cross-Sectional Evaluation of the Use of Artemisinin-Based Combination Therapy for Treatment of Malaria Infection at a Tertiary Hospital in Nigeria." Journal of Tropical Medicine 2018 (2018): 1–6. http://dx.doi.org/10.1155/2018/2025858.
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In 2005, Nigeria changed its antimalarial drug policy to Artemisinin-based Combination Therapies (ACTs) for the treatment of malaria infection, and it is imperative for prescribers to strictly comply with this guideline to harmonize malaria management practices within the country. This study aims to evaluate prescribers’ adherence with the National Antimalarial Treatment Guideline (NATG) in the treatment of malaria infections and to describe the determinants of antimalarial drugs coprescription with antibiotics at a tertiary hospital in Nigeria. A cross-sectional, retrospective study of antimalarial drug prescriptions of one-year period of 2013 was conducted. A simple method for assessing the quality of drug prescribing (DU90%) was adopted. Logistic regression was used to predict antimalarial drugs coprescription with antibiotics. Overall, 95.8% of the total prescriptions contained ACTs, out of which 80.8% were Artemether/Lumefantrine. However, adherence to NATG was 88.2% with an adjusted value of 100.0%. Age was the only predictor for antimalarial drugs coprescription with antibiotics. This study showed high concordance with NATG at the studied hospital. Age less than 5 years is a significant risk factor for antimalarial drugs coprescription with antibiotics.
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Suzuki, Hiroshi, Aiko Kume, and Maria Herbas. "Potential of Vitamin E Deficiency, Induced by Inhibition of α-Tocopherol Efflux, in Murine Malaria Infection." International Journal of Molecular Sciences 20, no. 1 (December 24, 2018): 64. http://dx.doi.org/10.3390/ijms20010064.
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Although epidemiological and experimental studies have suggested beneficial effects of vitamin E deficiency on malaria infection, it has not been clinically applicable for the treatment of malaria owing to the significant content of vitamin E in our daily food. However, since α-tocopherol transfer protein (α-TTP) has been shown to be a determinant of vitamin E level in circulation, manipulation of α-tocopherol levels by α-TTP inhibition was considered as a potential therapeutic strategy for malaria. Knockout studies in mice indicated that inhibition of α-TTP confers resistance against malaria infections in murines, accompanied by oxidative stress-induced DNA damage in the parasite, arising from vitamin E deficiency. Combination therapy with chloroquine and α-TTP inhibition significantly improved the survival rates in murines with malaria. Thus, clinical application of α-tocopherol deficiency could be possible, provided that α-tocopherol concentration in circulation is reduced. Probucol, a recently found drug, induced α-tocopherol deficiency in circulation and was effective against murine malaria. Currently, treatment of malaria relies on the artemisinin-based combination therapy (ACT); however, when mice infected with malarial parasites were treated with probucol and dihydroartemisinin, the beneficial effect of ACT was pronounced. Protective effects of vitamin E deficiency might be extended to manage other parasites in future.
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Björkman, Anders. "Malaria associated anaemia, drug resistance and antimalarial combination therapy." International Journal for Parasitology 32, no. 13 (December 2002): 1637–43. http://dx.doi.org/10.1016/s0020-7519(02)00192-3.
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Falilat Toyin AKINRULI, Veronica Oluwakemi OLUWASUSI, and Oluwafemi Ojo JULIUS. "Comparative efficacy of five brands of Arthemeter Combination Therapy (ACTS) purchased in Ekiti State, Nigeria." World Journal of Advanced Research and Reviews 15, no. 1 (July 30, 2022): 432–38. http://dx.doi.org/10.30574/wjarr.2022.15.1.0727.
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Malaria is one of the most severe public health problems and a leading cause of morbidity and mortality where children and pregnant women are the most affected groups. This may be as a result of resistant of malaria parasites which are mostly traceable to drug adulteration. In this study, Plasmodium berghei NK65, a rodent malaria parasite was used as a model organism to simulate human malaria parasite. The efficacy of five brands of arthemeter combination therapies (ACTs) purchased from pharmacy stores in Ekiti state were evaluated. The drugs were coded Art-Ar, Art-Ph, Art-Ki, Art- Na, and Art-Gy respectively. Twenty-one mice were constituted into seven different groups of three mice. Each mouse was inoculated inter-peritoneally with Plasmodium berghei NK65 and left for 7days for the parasite to manifest. The prepared drug solution was administered on five of the seven groups orally for 10 days, while the remaining groups were used as the positive and the negative control groups. One of the control groups was given chloroquine (positive) and the other normal saline (negative). The antimalarial efficacy of the drugs (ACTs) was determined by examining their influence on the increase or decrease in the number of parasites (parasitemia level). Giemsa stained thin blood smears from the tails were used to assess parasitemia level and the parasites clearance rate. Results show that the average parasite clearance rates were 14.1, 40.6, 25.3, 44.9 and 27.9 for Arthemeter coded as Art-Ar, Art-Ph, Art-Ki, Art- Na and Art-Gy respectively. All the brands significantly cleared all the parasites within 7-9days of the treatment, which shows that adulterated Arthemeter is not presently in the community studied. Therefore, arthemeter combination therapy is recommended as a drug of choice for the treatment of malaria fever in Ekiti State.
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Bell, Angus, and Daniela Boehm. "Anti-disease Therapy for Malaria - ‘Resistance Proof’?" Current Pharmaceutical Design 19, no. 2 (November 1, 2012): 300–306. http://dx.doi.org/10.2174/1381612811306020300.
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Yadav, Dharmendra K., Surendra Kumar, Mahesh K. Teli, Ravikant Yadav, and Sandeep Chaudhary. "Molecular Targets for Malarial Chemotherapy: A Review." Current Topics in Medicinal Chemistry 19, no. 10 (July 19, 2019): 861–73. http://dx.doi.org/10.2174/1568026619666190603080000.
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The malaria parasite resistance to the existing drugs is a serious problem to the currently used antimalarials and, thus, highlights the urgent need to develop new and effective anti-malarial molecules. This could be achieved either by the identification of the new drugs for the validated targets or by further refining/improving the existing antimalarials; or by combining previously effective agents with new/existing drugs to have a synergistic effect that counters parasite resistance; or by identifying novel targets for the malarial chemotherapy. In this review article, a comprehensive collection of some of the novel molecular targets has been enlisted for the antimalarial drugs. The targets which could be deliberated for developing new anti-malarial drugs could be: membrane biosynthesis, mitochondrial system, apicoplasts, parasite transporters, shikimate pathway, hematin crystals, parasite proteases, glycolysis, isoprenoid synthesis, cell cycle control/cycline dependent kinase, redox system, nucleic acid metabolism, methionine cycle and the polyamines, folate metabolism, the helicases, erythrocyte G-protein, and farnesyl transferases. Modern genomic tools approaches such as structural biology and combinatorial chemistry, novel targets could be identified followed by drug development for drug resistant strains providing wide ranges of novel targets in the development of new therapy. The new approaches and targets mentioned in the manuscript provide a basis for the development of new unique strategies for antimalarial therapy with limited off-target effects in the near future.
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Strangward, Patrick, Michael J. Haley, Manuel G. Albornoz, Jack Barrington, Tovah Shaw, Rebecca Dookie, Leo Zeef, et al. "Targeting the IL33–NLRP3 axis improves therapy for experimental cerebral malaria." Proceedings of the National Academy of Sciences 115, no. 28 (June 28, 2018): 7404–9. http://dx.doi.org/10.1073/pnas.1801737115.
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Cerebral malaria (CM) is a serious neurological complication caused by Plasmodium falciparum infection. Currently, the only treatment for CM is the provision of antimalarial drugs; however, such treatment by itself often fails to prevent death or development of neurological sequelae. To identify potential improved treatments for CM, we performed a nonbiased whole-brain transcriptomic time-course analysis of antimalarial drug chemotherapy of murine experimental CM (ECM). Bioinformatics analyses revealed IL33 as a critical regulator of neuroinflammation and cerebral pathology that is down-regulated in the brain during fatal ECM and in the acute period following treatment of ECM. Consistent with this, administration of IL33 alongside antimalarial drugs significantly improved the treatment success of established ECM. Mechanistically, IL33 treatment reduced inflammasome activation and IL1β production in microglia and intracerebral monocytes in the acute recovery period following treatment of ECM. Moreover, treatment with the NLRP3-inflammasome inhibitor MCC950 alongside antimalarial drugs phenocopied the protective effect of IL33 therapy in improving the recovery from established ECM. We further showed that IL1β release from macrophages was stimulated by hemozoin and antimalarial drugs and that this was inhibited by MCC950. Our results therefore demonstrate that manipulation of the IL33–NLRP3 axis may be an effective therapy to suppress neuroinflammation and improve the efficacy of antimalarial drug treatment of CM.
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Rocamora, Frances, and Elizabeth A. Winzeler. "Genomic Approaches to Drug Resistance in Malaria." Annual Review of Microbiology 74, no. 1 (September 8, 2020): 761–86. http://dx.doi.org/10.1146/annurev-micro-012220-064343.
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Although the last two decades have seen a substantial decline in malaria incidence and mortality due to the use of insecticide-treated bed nets and artemisinin combination therapy, the threat of drug resistance is a constant obstacle to sustainable malaria control. Given that patients can die quickly from this disease, public health officials and doctors need to understand whether drug resistance exists in the parasite population, as well as how prevalent it is so they can make informed decisions about treatment. As testing for drug efficacy before providing treatment to malaria patients is impractical, researchers need molecular markers of resistance that can be more readily tracked in parasite populations. To this end, much work has been done to unravel the genetic underpinnings of drug resistance in Plasmodium falciparum. The aim of this review is to provide a broad overview of common genomic approaches that have been used to discover the alleles that drive drug response phenotypes in the most lethal human malaria parasite.
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Pujiyanto, Mahendra, Zhaza Afililla, Lilik Maslachah, Thomas Valentinus Widiyatno, Mochamad Donny Koerniawan, Eko Agus Suyono, Arief Budiman, Ulfah Juniarti Siregar, and Lucia Tri Suwanti. "The Activity of Mixed Microalgae Polysaccharides from Indonesia as Anti-Malaria in Vitro." Jurnal Ilmiah Perikanan dan Kelautan 14, no. 2 (August 30, 2022): 396–403. http://dx.doi.org/10.20473/jipk.v14i2.34766.
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Highlight Research One of the content of microalgae that is beneficial for health is polysaccharides Polysaccharides of Indonesian microalgae can be promoted as anti-malarial Polysaccharides from Glagah, Spirulina and East Java microalgae inhibited the growth of plasmodium in vitro and had IC50 values of 3.18 µg/mL, 5.43µg/mL and 9.87 µg/mL, respectively Abstract Malaria is an infectious disease caused by protozoan parasites of the genus Plasmodium that categorized as deadliest diseases in the world. Artemisinin and its derivatives are still recommended drugs for malaria therapy, however, there have been indications that Plasmodium parasites are resistant to this drug. Therefore, a study on polysaccharides from microalgae may be a potential as bioactive compound for anti-malaria. The aim of this study was to determine the effectiveness of the mixed microalgae polysaccharides as anti-malarial in vitro. Polysaccharides were extracted from three microalgae Spirulina sp., mixed microalgae Glagah and mixed microalgae East Java using the alkaline extraction method. The anti-malarial activity test refers to the concentration of polysaccharides used in calculating the IC50 value by probit analysis. The concentration of polysaccharides of the three microalgae used were 0; 0.01; 0.01, 1, 10 and 100 µg/mL. The results showed that the IC50 values of polysaccharides of Glagah, Spirulina sp. and East Java microalgae were 3.18 µg/mL, 5.43µg/mL, and 9.87 µg/mL, respectively. In Conclusion, polysaccharides of Indonesian mixed microalgae can be promoted as anti-malarial.
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Elfawal, Mostafa A., Melissa J. Towler, Nicholas G. Reich, Pamela J. Weathers, and Stephen M. Rich. "Dried whole-plant Artemisia annua slows evolution of malaria drug resistance and overcomes resistance to artemisinin." Proceedings of the National Academy of Sciences 112, no. 3 (January 5, 2015): 821–26. http://dx.doi.org/10.1073/pnas.1413127112.
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Pharmaceutical monotherapies against human malaria have proven effective, although ephemeral, owing to the inevitable evolution of resistant parasites. Resistance to two or more drugs delivered in combination will evolve more slowly; hence combination therapies have become the preferred norm in the fight against malaria. At the forefront of these efforts has been the promotion of Artemisinin Combination Therapy, but despite these efforts, resistance to artemisinin has begun to emerge. In 2012, we demonstrated the efficacy of the whole plant (WP)—not a tea, not an infusion—as a malaria therapy and found it to be more effective than a comparable dose of pure artemisinin in a rodent malaria model. Here we show that WP overcomes existing resistance to pure artemisinin in the rodent malaria Plasmodiumyoelii. Moreover, in a long-term artificial selection for resistance in Plasmodium chabaudi, we tested resilience of WP against drug resistance in comparison with pure artemisinin (AN). Stable resistance to WP was achieved three times more slowly than stable resistance to AN. WP treatment proved even more resilient than the double dose of AN. The resilience of WP may be attributable to the evolutionary refinement of the plant’s secondary metabolic products into a redundant, multicomponent defense system. Efficacy and resilience of WP treatment against rodent malaria provides compelling reasons to further explore the role of nonpharmaceutical forms of AN to treat human malaria.
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Ujuamala Uloma Ezeani, Penaere Theresa Osahon, and Michael Chukwudi Ezeani. "Pattern of anti-malarial drugs and artemether combination therapy adherence in an institution based medical centre, Nigeria." World Journal of Advanced Research and Reviews 8, no. 3 (December 30, 2020): 162–70. http://dx.doi.org/10.30574/wjarr.2020.8.3.0437.
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The change in policy guidelines for treating uncomplicated malaria became necessary because the therapeutic efficacy of chloroquine and SP had deteriorated. Hence compliance is a necessity to enable effective check on malaria. This work was carried out to evaluate antimalaria drug prescription and to update its usage in line with WHO guideline on Artemeter Combination therapy in a university based medical center. We utilized descriptive, cross-sectional, retrospective study of antimalaria prescriptions purposely carried out among male and female outpatients with mean age of 22.4±2.8 at a University health facility. This comprised all outpatients prescriptions that contained at least one antimalarial drug filed from October 2018 to September 2019. Systematic sampling was used to select the prescriptions. Based on the total number of 1250 prescriptions containing at least one antimalarial drug, a sampling interval of 5 was calculated and simple balloting was used for the first pick. A total number of two hundred and fifty (250) prescriptions containing at least one antimalarial drug were selected for the study. Out of 250 antimalaria prescriptions, usage of ACT class of Artemeter lumefantrine, Artemeter Amodiaquine and Artemeter Piparaqiune were recorded at 45.6%, 10.4% and 9.6% respectively. Triple combination Artemeter lumefantrine and Sulphadoxine-Pyrimethamine was recorded at 20.4% while Sulphadoxine-Pyrimethamine was recorded at 4%. Combination of antimalarial drugs with antibiotics was recorded at 31.2%. This study showed compliance with National Antimalarial Treatment Guideline for the treatment of malaria infection as it regards the use of artemisinin-based combination therapy. The frequency usage of artemeter lumefantrine was proceeding among other ACTs. The frequency in co-prescription of antibiotics with anti-malaria should be guarded to comply with WHO recommendation.
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FALAJIKI, Y. F., O. AKINOLA, O. O. ABIODUN, C. T. HAPPI, A. SOWUNMI, and G. O. GBOTOSHO. "Amodiaquine–Ciprofloxacin: a potential combination therapy against drug resistant malaria." Parasitology 142, no. 6 (March 4, 2015): 849–54. http://dx.doi.org/10.1017/s0031182015000062.
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SUMMARYEmergence of malaria parasites resistant to artemisinin necessitates the need for development of new antimalarial therapies. Ciprofloxacin (CFX) a second generation quinolone antibiotic possesses some antimalarial activities. We investigated the in vivo antimalarial activities of CFX in combination with amodiaquine in mice infected with chloroquine-resistant Plasmodium berghei ANKA. Animals were treated orally with 80 or 160 mg kg−1 body weight of CFX alone given twice daily or in combination with amodiaquine (AQ) 10 mg kg−1 body weight. Parasitological activity and survival of the animals were assessed over 21 days. Peak parasitaemia in the untreated control group was 72·51%. Treatment with AQ alone resulted in clearance of parasitaemia by day 4 while treatment with CFX 80 and 160 mg kg−1 alone suppressed parasitaemia by 13·94–54·64% and 35·6–92·7%, respectively. However, the combination of CFX with AQ significantly enhanced response of infection in the animals to treatment (P < 0·05) resulting in complete resolution of parasitaemia throughout follow up period with CFX 160 mg kg−1, delayed recrudescence time with CFX 80 mg kg−1 and significant increase in survival rate of the animals. The results demonstrate beneficial interaction between AQ and CFX which may provide a clinically relevant antimalarial/antibiotic therapeutic option in the management of malaria.
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Uriel, A., and P. Lewthwaite. "Malaria therapy in HIV: drug interactions between nevirapine and quinine." International Journal of STD & AIDS 22, no. 12 (December 2011): 768. http://dx.doi.org/10.1258/ijsa.2009.009489.
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Chakim, Irfanul, and Tepanata Pumpaibool. "Drug Metabolite as a Novel Tool for Measuring Antimalarial Drug Adherence." Open Public Health Journal 11, no. 1 (June 29, 2018): 288–97. http://dx.doi.org/10.2174/1874944501811010288.
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Malaria has been a major public health problem worldwide. The burden of malaria has been reduced by the adoption of Artemisinin-Combination Therapy (ACT) followed by primaquine dosage in malaria-endemic countries. However, evidences of non-adherence behavior lead to the discovery of antimalarial drug adherence to ensure a successful and satisfactory treatment of ACT, since it is the only available antimalarial drugs against asexual form of the parasite. Unstandardized questionnaires and limited effective alternative approaches have been the major obstacles to measure adherence. With rapid development of pharmacokinetic research, public health researchers can adopt the approach to measure adherence. Notwithstanding, the current structured questionnaire has explained in detail that the measurement and classification of adherence have produced satisfactory results. However, it is subject to social desirability bias. Therefore, in this review, we offer a new strategy combining structured questionnaire and drug metabolite as a novel consensus which eliminates biases. A new classification of adherence and graphical representation of practical strategy and other important factors are provided in this review. Thus, it initiates further works to conduct an intervention program to increase adherence level. Additionally, adherence behavior prevents the development of drug resistance and its spread, increases satisfactory cure rate and inhibits transmission by eliminating gametocyte inside host’s body.
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Ojurongbe, Olusola, Olubunmi A. Lawal, Oyindamola O. Abiodun, John A. Okeniyi, Ayobami J. Oyeniyi, and Oyeku A. Oyelami. "Efficacy of artemisinin combination therapy for the treatment of uncomplicated falciparum malaria in Nigerian children." Journal of Infection in Developing Countries 7, no. 12 (December 15, 2013): 975–82. http://dx.doi.org/10.3855/jidc.3058.
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Introduction: The development and spread of Plasmodium falciparum resistance to most commonly used antimalarials remain a major challenge in the control of malaria. Constant monitoring of drug efficacy is an important tool in establishing rational antimalarial drug policies. Methodology: A randomized comparative study was conducted at the Wesley Guild Hospital, Ilesa, Nigeria between February 2010 and September 2011 comparing the efficacy and safety of artemether-lumefantrine (Coartem) and fixed dose of artesunate plus amodiaquine (Larimal) in the treatment of uncomplicated P. falciparum malaria in children betweem 6 and 144 months of age. P. falciparum malaria parasitemia was assessed by microscopy and rapid diagnostic test. Drugs were administered according to age for three days under supervision. The primary efficacy endpoint was a day 28 PCR-corrected parasitological cure. Results: A total of 182 patients were enrolled in the two treatment groups, Coartem (n = 101) and Larimal (n = 81), and tested after 28 days. In the intention-to-treat population, Coartem (n= 101) and Larimal (n= 81) had a PCR-corrected cure rate of 98% and 100% respectively, while in the per-protocol population, Coartem (n = 89) and Larimal (n = 71) both had a PCR-corrected cure rate of 100% at day 28. Although parasite and fever clearance time was faster in the Larimal group, no significant difference was observed between the two drugs. No serious adverse effects were reported. Conclusion: Five years after being introduced in Nigeria, both Coartem and Larimal have been shown to be safe and highly effective in the treatment of uncomplicated P. falciparum malaria in children.
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Bergquist, Robert, and Hala Elmorshedy. "Artemether and Praziquantel: Origin, Mode of Action, Impact, and Suggested Application for Effective Control of Human Schistosomiasis." Tropical Medicine and Infectious Disease 3, no. 4 (December 19, 2018): 125. http://dx.doi.org/10.3390/tropicalmed3040125.
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The stumbling block for the continued, single-drug use of praziquantel (PZQ) against schistosomiasis is less justified by the risk of drug resistance than by the fact that this drug is inactive against juvenal parasites, which will mature and start egg production after chemotherapy. Artemisinin derivatives, currently used against malaria in the form of artemisinin-based combination therapy (ACT), provide an opportunity as these drugs are not only active against malaria plasmodia, but surprisingly also against juvenile schistosomes. An artemisinin/PZQ combination would be complimentary, and potentially additive, as it would kill two schistosome life cycle stages and thus confer a transmission-blocking modality to current chemotherapy. We focus here on single versus combined regimens in endemic settings. Although the risk of artemisinin resistance, already emerging with respect to malaria therapy in Southeast Asia, prevents use in countries where ACT is needed for malaria care, an artemisinin-enforced praziquantel treatment (APT) should be acceptable in North Africa (including Egypt), the Middle East, China, and Brazil, as these countries are not endemic for malaria. Thanks to recent progress with respect to high-resolution diagnostics, based on circulating schistosome antigens in humans and molecular approaches for snail surveys, it should be possible to keep areas scheduled for schistosomiasis elimination under surveillance, bringing rapid response to bear on problems arising. The next steps would be to investigate where and for how long APT should be applied to make a lasting impact. A large-scale field trial in an area with modest transmission should tell how apt this approach is.
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Chan, Wilson W., Divya Virmani, and Dylan R. Pillai. "Artemisinin Combination Therapy Can Result in Clinical Failure If Oral Therapy Is Not Directly Observed." Canadian Journal of Infectious Diseases and Medical Microbiology 24, no. 4 (2013): 215–16. http://dx.doi.org/10.1155/2013/427910.
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Intravenous artesunate therapy is the first-line therapy for severe malaria, and is highly efficacious when used in combination with an oral partner drug such as doxycycline or atovaquone-proguanil. However, treatment failure occurs routinely with artesunate monotherapy due to the very short half-life of this drug. In North America, experience with artesunate is limited. With the pressure to discharge patients early, administration of the essential oral partner drug is often left to the discretion of the patient. Thus, treatment failure may be commonplace if nonadherence is a factor, as was observed in the case described in the present report.
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Adamu, A., U. Ango, M. Oche, M. Bello, M. Ali, I. Ibrahim, M. Umar, et al. "PHYSICIANS' COMPLIANCE WITH ANTI-MALARIAL TREATMENT GUIDELINES AMONG UNDER FIVE CHILDREN ATTENDING SECONDARY HEALTH FACILITIES IN SOKOTO METROPOLIS." European Journal of Health Sciences 6, no. 3 (September 22, 2021): 22–32. http://dx.doi.org/10.47672/ejhs.802.
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Introduction: Rational use of drugs against most common and life‑threatening tropical diseases such as malaria remains a huge challenge, particularly in sub-Saharan African region. The correct use of antimalarial drugs is the key not only to therapeutic success but also to deterring the spread of drug resistance malaria.
Aims: To assess the physicians’ compliance with the national anti’-malaria treatment guidelines among Under five (U-5) years children in secondary health facilities in Sokoto metropolis.
Methods: This was a cross-sectional study conducted as an exit interview among 292 mothers/caregivers of febrile U-5 children with antimalarial prescription, that presented to the out-patient clinics of the selected secondary health facilities in Sokoto metropolis. Simple random sampling technique using balloting option was used to select 2 secondary Health facilities in the metropolis, Proportionate allocation was done to allocate study subjects to the selected Health facilities based on average weekly outpatient attendance. The data was collected using an interviewer-administered questionnaire. Descriptive statistics was used to analysed data using IBM SPSS version 22.
Results: Of the 292 children, only 115(39.4%) had malaria parasite test requested by the physician, out of which 63(54.8) had microscopy, while 52(45.2) of the children had malaria Rapid Diagnostic Test (mRDT). One hundred and eighty-five (65.1%) of the children were treated presumptively with anti-malarial drugs. Artemisinin based Combination Therapy (ACT) was prescribed in 221(77.8%) of the under-fives. The commonest prescribed ACT was Artemether-Lumefantrine in 113(77.4%) of the children. Majority 263(92.6%) of the prescriptions were in brand names.
Recommendation: The physicians’ compliance with national malaria treatment guidelines using the proportion of U-5 children was suboptimal. There was over prescription of anti-malarial drugs, as majority of the patients treated for malaria had no laboratory evidence for the treatment. However, compliance with the use of ACT was good. This study shows also suboptimal compliance with WHO prescribing indicators with respect to prescription in generic names. Regular training of the health care providers by the government is recommended to improve adherence to antimalarial treatment guideline.
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Talisuna, Ambrose O., Peter Bloland, and Umberto D’Alessandro. "History, Dynamics, and Public Health Importance of Malaria Parasite Resistance." Clinical Microbiology Reviews 17, no. 1 (January 2004): 235–54. http://dx.doi.org/10.1128/cmr.17.1.235-254.2004.
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SUMMARY Despite considerable efforts, malaria is still one of the most devastating infectious diseases in the tropics. The rapid spread of antimalarial drug resistance currently compounds this grim picture. In this paper, we review the history of antimalarial drug resistance and the methods for monitoring it and assess the current magnitude and burden of parasite resistance to two commonly used drugs: chloroquine and sulfadoxine-pyrimethamine. Furthermore, we review the factors involved in the emergence and spread of drug resistance and highlight its public health importance. Finally, we discuss ways of dealing with such a problem by using combination therapy and suggest some of the research themes needing urgent answers.
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Peter, Sijongesonke, Siphesihle Jama, Sibusiso Alven, and Blessing A. Aderibigbe. "Artemisinin and Derivatives-Based Hybrid Compounds: Promising Therapeutics for the Treatment of Cancer and Malaria." Molecules 26, no. 24 (December 11, 2021): 7521. http://dx.doi.org/10.3390/molecules26247521.
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Cancer and malaria are major health conditions around the world despite many strategies and therapeutics available for their treatment. The most used strategy for the treatment of these diseases is the administration of therapeutic drugs, which suffer from several shortcomings. Some of the pharmacological limitations associated with these drugs are multi-drug resistance, drug toxicity, poor biocompatibility and bioavailability, and poor water solubility. The currently ongoing preclinical studies have demonstrated that combination therapy is a potent approach that can overcome some of the aforementioned limitations. Artemisinin and its derivatives have been reported to exhibit potent efficacy as anticancer and antimalarial agents. This review reports hybrid compounds containing artemisinin scaffolds and their derivatives with promising therapeutic effects for the treatment of cancer and malaria.
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Bakhiet, Amani M. A., Mohamed H. Abdelraheem, Amani Kheir, Samia Omer, Linda Gismelseed, Abdel-Muhsin A. Abdel-Muhsin, Ahmed Naiem, et al. "Evolution of Plasmodium falciparum drug resistance genes following artemisinin combination therapy in Sudan." Transactions of The Royal Society of Tropical Medicine and Hygiene 113, no. 11 (August 1, 2019): 693–700. http://dx.doi.org/10.1093/trstmh/trz059.
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Abstract Background Malaria control efforts in Sudan rely heavily on case management. In 2004, health authorities adopted artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria. However, some recent surveys have reported ACT failure and a prevalent irrational malaria treatment practice. Here we examine whether the widespread use of ACT and failure to adhere to national guidelines have led to the evolution of drug resistance genes. Methods We genotyped known drug resistance markers (Pfcrt, Pfmdr-1, Pfdhfr, Pfdhps, Pfk13 propeller) and their flanking microsatellites among Plasmodium falciparum isolates obtained between 2009 and 2016 in different geographical regions in Sudan. Data were then compared with published findings pre-ACT (1992–2003). Results A high prevalence of Pfcrt76T, Pfmdr-1-86Y, Pfdhfr51I, Pfdhfr108N, Pfdhps37G was observed in all regions, while no Pfk13 mutations were detected. Compared with pre-ACT data, Pfcrt-76T and Pfmdr-1-86Y have decayed, while Pfdhfr-51I, Pfdhfr-108N and Pfdhps-437G strengthened. Haplotypes Pfcrt-CVIET, Pfmdr-1-NFSND/YFSND, Pfdhfr-ICNI and Pfdhps-SGKAA predominated in all sites. Microsatellites flanking drug resistance genes showed lower diversity than neutral ones, signifying high ACT pressure/selection. Conclusions Evaluation of P. falciparum drug resistance genes in Sudan matches the drug deployment pattern. Regular monitoring of these genes, coupled with clinical response, should be considered to combat the spread of ACT resistance.
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Strangward, Patrick, and Kevin Couper. "Systems-based identification of new adjunct therapies for treatment of malaria-induced cerebral pathology." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 134.13. http://dx.doi.org/10.4049/jimmunol.196.supp.134.13.
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Abstract Cerebral Malaria (CM) is a severe neurological complication of Plasmodium falciparum infection characterised by abnormal posturing, seizures and coma. Current treatment involves the administration of anti-parasitic drugs, and fails to prevent mortality in 10–20% of cases. Furthermore, up to a quarter of effectively treated individuals exhibit long-term neurological dysfunction after an episode of CM. Crucially, we lack understanding of the factors that govern a successful or unsuccessful outcome to current treatment. Therefore, the aim of this study was to utilise the murine experimental model of CM (ECM) to further our understanding of the mechanism(s) that determine successful drug therapy of CM, in order to aid development of specific adjunct therapies. C57BL/6 mice were infected with Plasmodium berghei ANKA and then treated with anti-parasitic drugs at the onset of mild neurological dysfunction. Survival was ~80% in drug treated mice, with histological examination indicating attenuation of oedema as a key feature in mice that respond successfully to drug therapy. Additionally, whole brain transcriptomics demonstrated unique cerebral RNA signatures in mice at the point of drug treatment, post successful drug treatment and in the absence of drug treatment. Moreover, these data implicated several pathways relating to endothelial permeability as significant in mice that succumb to ECM. The results of this study provide important new information on pathways amenable to therapeutic modulation to aid treatment of CM.
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Guo, Jin, Armand W. Guiguemde, Annael Bentura-Marciano, Julie Clark, Richard K. Haynes, Wing-Chi Chan, Ho-Ning Wong, Nicholas H. Hunt, R. Kiplin Guy, and Jacob Golenser. "Synthesis of Artemiside and Its Effects in Combination with Conventional Drugs against Severe Murine Malaria." Antimicrobial Agents and Chemotherapy 56, no. 1 (October 17, 2011): 163–73. http://dx.doi.org/10.1128/aac.05006-11.
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ABSTRACTThis research describes the use of novel antimalarial combinations of the new artemisinin derivative artemiside, a 10-alkylamino artemisinin. It is a stable, highly crystalline compound that is economically prepared from dihydroartemisinin in a one-step process. Artemiside activity was more pronounced than that of any antimalarial drug in use, both inPlasmodium falciparumculture andin vivoin a murine malaria model depicting cerebral malaria (CM).In vitrohigh-throughput testing of artemiside combinations revealed a large number of conventional antimalarial drugs with which it was additive. Following monotherapy in mice, individual drugs reduced parasitemias to nondetectable levels. However, after a period of latency, parasites again were seen and eventually all mice became terminally ill. Treatment with individual drugs did not prevent CM in mice with recrudescent malaria, except for piperaquine at high concentrations. Even when CM was prevented, the mice developed later of severe anemia. In contrast, most of the mice treated with drug combinations survived. A combination of artemiside and mefloquine or piperaquine may confer an optimal result because of the longer half life of both conventional drugs. The use of artemiside combinations revealed a significant safety margin of the effective artemiside doses. Likewise, a combination of 1.3 mg/kg of body weight artemiside and 10 mg/kg piperaquine administered for 3 days from the seventh day postinfection was completely curative. It appears possible to increase drug concentrations in the combination therapy without reaching toxic levels. Using the drug combinations as little as 1 day before the expected death of control animals, we could prevent further parasite development and death due to CM or anemic malaria. Earlier treatment may prevent cognitive dysfunctions which might occur after recovery from CM.
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Abdelbagi Elfadil Mousa, Hamoud Abdullah Alsamhan, Hafsa Elawd Mohamed Ahmed, Mohamed Abd Rhman Adris Abdallah, Osman Mohamed Elhadi Abdalla, Taroob Abdalwahab Abdalhameed, Hamed Alneel Albagir Ahmed, et al. "Plasmodium falciparum resistance and malaria presentation in children at Dongola specialist hospital: A prospective cohort study." Journal of the Pakistan Medical Association 72, no. 4 (April 5, 2022): 649–53. http://dx.doi.org/10.47391/jpma.1310.
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Objective: To provide evidence about the susceptibility of anti-malarial drugs, and to identify the clinical features of the disease in children. Method: The prospective observational comparative study was conducted at the Dongola Specialist Hospital, Dunqulah, Sudan, from February 2016 to February 2017, and comprised children aged <16 years with bodyweight >5kg who had malaria. The subjects were enrolled into group 1, which received treatment based on physician’s discretion, and group 2, which received treatment in accordance with the national guideline. The follow-up was conducted on days 3, 7 and 14 to identify cases as early treatment failure, late treatment failure, or treatment success. Data were analysed in terms of frequencies and percentages using statistical analysis software R version 3.1.2. Results: Of the 120 children, 60(50%) were in each of the two groups. Overall, 63(52.5%) were aged 1-6 years, 66(55%) were males, and 42(35%) were exposed to malaria for the first time. Post-treatment test was negative for all 120(100%) the subjects in both the groups. showing no inter-group difference. Conclusion: Although resistance to combination therapy was not detected, it remains extremely important to remain vigilant for the emergence of resistance in the future. Key Words: Child, Drug resistance, Malaria, Sudan. Continue...
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Kumi, Ransford Oduro, Belinda Oti, Nader E. Abo-Dya, Mohamed Issa Alahmdi, and Mahmoud E. S. Soliman. "Bridging the Gap in Malaria Parasite Resistance, Current Interventions, and the Way Forward from in Silico Perspective: A Review." Molecules 27, no. 22 (November 16, 2022): 7915. http://dx.doi.org/10.3390/molecules27227915.
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The past decade has seen most antimalarial drugs lose their clinical potency stemming from parasite resistance. Despite immense efforts by researchers to mitigate this global scourge, a breakthrough is yet to be achieved, as most current malaria chemotherapies suffer the same fate. Though the etiology of parasite resistance is not well understood, the parasite’s complex life has been implicated. A drug-combination therapy with artemisinin as the central drug, artemisinin-based combination therapy (ACT), is currently the preferred malaria chemotherapy in most endemic zones. The emerging concern of parasite resistance to artemisinin, however, has compromised this treatment paradigm. Membrane-bound Ca2+-transporting ATPase and endocytosis pathway protein, Kelch13, among others, are identified as drivers in plasmodium parasite resistance to artemisinin. To mitigate parasite resistance to current chemotherapy, computer-aided drug design (CADD) techniques have been employed in the discovery of novel drug targets and the development of small molecule inhibitors to provide an intriguing alternative for malaria treatment. The evolution of plasmepsins, a class of aspartyl acid proteases, has gained tremendous attention in drug discovery, especially the non-food vacuole. They are expressed at multi-stage of the parasite’s life cycle and involve in hepatocytes’ egress, invasion, and dissemination of the parasite within the human host, further highlighting their essentiality. In silico exploration of non-food vacuole plasmepsin, PMIX and PMX unearthed the dual enzymatic inhibitory mechanism of the WM382 and 49c, novel plasmepsin inhibitors presently spearheading the search for potent antimalarial. These inhibitors impose structural compactness on the protease, distorting the characteristic twist motion. Pharmacophore modeling and structure activity of these compounds led to the generation of hits with better affinity and inhibitory prowess towards PMIX and PMX. Despite these headways, the major obstacle in targeting PM is the structural homogeneity among its members and to human Cathepsin D. The incorporation of CADD techniques described in the study at early stages of drug discovery could help in selective inhibition to augment malaria chemotherapy.
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Oboh, Mary Aigbiremo, Daouda Ndiaye, Hiasindh Ashmi Antony, Aida Sadikh Badiane, Upasana Shyamsunder Singh, Nazia Anwar Ali, Praveen Kumar Bharti, and Aparup Das. "Status of Artemisinin Resistance in Malaria Parasite Plasmodium falciparum from Molecular Analyses of the Kelch13 Gene in Southwestern Nigeria." BioMed Research International 2018 (October 3, 2018): 1–5. http://dx.doi.org/10.1155/2018/2305062.
Full textAbstract:
Evolution and spread of malaria parasite Plasmodium falciparum capable of evading antimalarials are the prime concern to malaria control. The currently effective drug, artemisinin (ART), is under threat due to detection of ART-resistant P. falciparum parasites in the Southeast Asian countries. It has been shown that amino acid (AA) mutations at the P. falciparum Kelch13 (Pfk13) gene provide resistance to ART. Nigeria, a part of the Sub-Saharan Africa, is highly endemic to malaria, contributing quite significantly to malaria, and resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) combination drugs has already been reported. Since artemisinin combined therapy (ACT) is the first-line drug for treatment of uncomplicated malaria in Nigeria and five amino acid mutations have been validated in the Pfk13 gene alongside with candidate mutations for ART resistance, we performed molecular surveillance for mutations (following PCR and DNA sequence analyses) in this gene from two southwestern states of Nigeria. Statistical analyses of DNA sequences were also performed following different evolutionary models. None of the different validated and candidate AA mutations of Pfk13 gene conferring resistance to ART could be detected in P. falciparum sampled in the two southwestern states of Nigeria. In addition, DNA sequencing and sequence analyses indicated neither evolutionary selection pressure on the Pfk13 gene nor association of mutations in Pfk13 gene with mutations of other three genes conferring resistance to CQ and SP. Therefore, based on the monomorphism at the Pfk13 gene and nonassociation of mutations of this gene with mutations in three other drug-resistant genes in malaria parasite P. falciparum, it can be proposed that malaria public health is not under immediate threat in southwestern Nigeria concerning ART resistance.
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Ochora, Douglas O., Esezah K. Kakudidi, Jane Namukobe, Perpetua Ipulet, Dancan M. Wakoli, Winnie Okore, Edwin W. Mwakio, et al. "Synergism in Antiplasmodial Activities of Artemether and Lumefantrine in Combination with Securidaca longipedunculata Fresen (Polygalaceae)." Plants 11, no. 1 (December 24, 2021): 47. http://dx.doi.org/10.3390/plants11010047.
Full textAbstract:
Malaria is the most lethal parasitic disease in the world. The frequent emergence of resistance by malaria parasites to any drug is the hallmark of sustained malaria burden. Since the deployment of artemisinin-based combination therapies (ACTs) it is clear that for a sustained fight against malaria, drug combination is one of the strategies toward malaria elimination. In Sub-Saharan Africa where malaria prevalence is the highest, the identification of plants with a novel mechanism of action that is devoid of cross-resistance is a feasible strategy in drug combination therapy. Thus, artemether and lumefantrine were separately combined and tested with extracts of Securidaca longipedunculata, a plant widely used to treat malaria, at fixed extract–drug ratios of 4:1, 3:1, 1:1, 1:2, 1:3, and 1:4. These combinations were tested for antiplasmodial activity against three strains of Plasmodium falciparum (W2, D6, and DD2), and seven field isolates that were characterized for molecular and ex vivo drug resistance profiles. The mean sum of fifty-percent fractional inhibition concentration (FIC50) of each combination and singly was determined. Synergism was observed across all fixed doses when roots extracts were combined with artemether against D6 strain (FIC50 0.403 ± 0.068) and stems extract combined with lumefantrine against DD2 strain (FIC50 0.376 ± 0.096) as well as field isolates (FIC50 0.656 ± 0.067). Similarly, synergism was observed in all ratios when leaves extract were combined with lumefantrine against W2 strain (FIC50 0.456 ± 0.165). Synergism was observed in most combinations indicating the potential use of S. longipedunculata in combination with artemether and lumefantrine in combating resistance.
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Schumacher, Richard-Fabian, and Elena Spinelli. "MALARIA IN CHILDREN." Mediterranean Journal of Hematology and Infectious Diseases 4, no. 1 (November 7, 2012): e2012073. http://dx.doi.org/10.4084/mjhid.2012.073.
Full textAbstract:
This review is focused on childhood specific aspects of malaria, especially in resource-poor settings. We summarise the actual knowledge in the field of epidemiology, clinical presentation, diagnosis, management and prevention.These aspects are important as malaria is responsible for almost a quarter of all child death in sub-Saharan Africa. Malaria control is thus one key intervention to reduce childhood mortality, especially as malaria is also an important risk factor for other severe infections, namely bacteraemia.In children symptoms are more varied and often mimic other common childhood illness, particularly gastroenteritis, meningitis/encephalitis, or pneumonia. Fever is the key symptom, but the characteristic regular tertian and quartan patterns are rarely observed. There are no pathognomonic features for severe malaria in this age group. The well known clinical (fever, impaired consciousness, seizures, vomiting, respiratory distress) and laboratory (severe anaemia, thrombocytopenia, hypoglycaemia, metabolic acidosis, and hyperlactataemia) features of severe falciparum malaria in children, are equally typical for severe sepsis.Appropriate therapy (considering species, resistance patterns and individual patient factors) – possibly a drug combination of an artemisinin derivative with a long-acting antimalarial drug - reduces treatment duration to only three days and should be urgently started.While waiting for the results of ongoing vaccine trials, all effort should be made to better implement other malaria-control measures like the use of treated bed-nets and new chemoprophylaxis regimens.
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Akanni, O. Ifeoluwa, J. O. Ehinmidu, and R. O. Bolaji. "Evaluation of antimalarial prescription pattern and susceptibility of Plasmodium falciparum isolates in Kaduna, Nigeria." International Journal of Biological and Chemical Sciences 13, no. 7 (February 13, 2020): 3398–410. http://dx.doi.org/10.4314/ijbcs.v13i7.34.
Full textAbstract:
Nigeria carries the highest burden of malaria in terms of morbidity and mortality. This is compounded by continuous resistance of Plasmodium falciparum to antimalarial drugs. This study was designed to evaluate the profile of malaria patients’ antimalarial drug prescription and in vitro susceptibility of P. falciparum isolates to commonly prescribed antimalarial drugs in Kaduna, Nigeria. Three years’ records of patients antimalarial drug prescriptions were collated (2013 to 2015) and the in vitro antimalarial agent susceptibility was determined for 28 clinical isolates using WHO Mark III microtest. Artemisinin-based combination therapy (ACT) was the most prescribed antimalarial for the period under review (92.3-93.7%). Among the ACTs, Artemether-lumefantrine was most prescribed. Of the 28 P. falciparum isolates evaluated, 3 (10.71%) were resistant to chloroquine with a median IC50 of 4.82μM (4.60-8.14μM), while five (17.86%) were resistant to mefloquine with a median IC50 of 25μM (10.3-41μM), 7(25.00%) to artemether with a median IC50 of 2.69μM (2.09-8.77μM), 9 (32.14%) to artesunate-mefloquine combination with a median IC50 of 9.0μM (7.98-35μM) and to artesunate, 11(39.29%) were resistant with a median IC50 of 2.4μM (1.56-5.65μM). This result shows a decline in resistance of P. falciparum to chloroquine compared to period prior to artemisinin-combination therapy as well as reduced susceptibility to artesunate and artemether. Further in vitro and in vivo monitoring will be required to inform antimalarial drug policy change.Keywords: Antimalarial, Artemisinin-combination therapy, resistance, susceptibility, microtest.
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Badeliya, Sandip N., Pankaj P. Kapupara, Navneet F. Chauhan, and Ishan I. Panchal. "A contemporary chemical entities infiltrating in the antimalarial therapy era: a comprehensive review." Folia Medica 63, no. 5 (October 31, 2021): 637–46. http://dx.doi.org/10.3897/folmed.63.e58995.
Full textAbstract:
Malaria, a life-threatening disease, is caused by parasitic single-celled microorganisms. It is specifically transmitted by the anopheles female mosquito of the Plasmodium family. There are a lot of drugs available in the market to treat this life-challenging disease. Chloroquine, a cheaper molecule that is available worldwide, is one of them. Drug resistance has been observed with chloroquine as well as with some other quinine derivatives and with artemisinin derivatives in the southeast region of Asia in countries like Cambodia, Thailand, Myanmar, and Vietnam country since 1957. After 1970, the drug resistance has been further increased and it has been expanded in several localities of India. Also, antimalarial agents, particularly chloroquine, have so many side effects such as nausea, vomiting, blurred vision, abdominal cramps, diarrhea, headache, appetite loss, deprivation of hearing, skin color change, baldness, reduced body weight, and seizures. Furthermore, this drug cannot be given to pregnant women. Hence, it is the right time to design and develop newer antimalarial agents so that this kind of drug resistance, as well as side effects of the drugs, can be overcome.
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Neto, Zoraima, Marta Machado, Ana Lindeza, Virgílio do Rosário, Marcos L. Gazarini, and Dinora Lopes. "Treatment ofPlasmodium chabaudiParasites with Curcumin in Combination with Antimalarial Drugs: Drug Interactions and Implications on the Ubiquitin/Proteasome System." Journal of Parasitology Research 2013 (2013): 1–11. http://dx.doi.org/10.1155/2013/429736.
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Antimalarial drug resistance remains a major obstacle in malaria control. Evidence from Southeast Asia shows that resistance to artemisinin combination therapy (ACT) is inevitable. Ethnopharmacological studies have confirmed the efficacy of curcumin againstPlasmodiumspp. Drug interaction assays between curcumin/piperine/chloroquine and curcumin/piperine/artemisinin combinations and the potential of drug treatment to interfere with the ubiquitin proteasome system (UPS) were analyzed.In vivoefficacy of curcumin was studied in BALB/c mice infected withPlasmodium chabaudiclones resistant to chloroquine and artemisinin, and drug interactions were analyzed by isobolograms. Subtherapeutic doses of curcumin, chloroquine, and artemisinin were administered to mice, and mRNA was collected following treatment for RT-PCR analysis of genes encoding deubiquitylating enzymes (DUBs). Curcumin was found be nontoxic in BALB/c mice. The combination of curcumin/chloroquine/piperine reduced parasitemia to 37% seven days after treatment versus the control group’s 65%, and an additive interaction was revealed. Curcumin/piperine/artemisinin combination did not show a favorable drug interaction in this murine model of malaria. Treatment of mice with subtherapeutic doses of the drugs resulted in a transient increase in genes encoding DUBs indicating UPS interference. If curcumin is to join the arsenal of available antimalarial drugs, future studies exploring suitable drug partners would be of interest.
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Zirkel, J., A. Cecil, F. Schäfer, S. Rahlfs, A. Ouedraogo, K. Xiao, S. Sawadogo, B. Coulibaly, K. Becker, and T. Dandekar. "Analyzing Thiol-Dependent Redox Networks in the Presence of Methylene Blue and Other Antimalarial Agents with RT-PCR-Supported in silico Modeling." Bioinformatics and Biology Insights 6 (January 2012): BBI.S10193. http://dx.doi.org/10.4137/bbi.s10193.
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Background In the face of growing resistance in malaria parasites to drugs, pharmacological combination therapies are important. There is accumulating evidence that methylene blue (MB) is an effective drug against malaria. Here we explore the biological effects of both MB alone and in combination therapy using modeling and experimental data. Results We built a model of the central metabolic pathways in P. falciparum. Metabolic flux modes and their changes under MB were calculated by integrating experimental data (RT-PCR data on mRNAs for redox enzymes) as constraints and results from the YANA software package for metabolic pathway calculations. Several different lines of MB attack on Plasmodium redox defense were identified by analysis of the network effects. Next, chloroquine resistance based on pfmdr/ and pfcrt transporters, as well as pyrimethamine/sulfadoxine resistance (by mutations in DHF/DHPS), were modeled in silico. Further modeling shows that MB has a favorable synergism on antimalarial network effects with these commonly used antimalarial drugs. Conclusions Theoretical and experimental results support that methylene blue should, because of its resistance-breaking potential, be further tested as a key component in drug combination therapy efforts in holoendemic areas.