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Yusuf, Yenni. "ANTI-MALARIAL DRUG RESISTANCE." Majalah Kedokteran Andalas 37, no. 1 (May 3, 2015): 64. http://dx.doi.org/10.22338/mka.v37.i1.p64-69.2014.
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AbstrakTujuan studi ini adalah untuk menjelaskan mekanisme resistensi parasit malaria danusaha-usaha yang dapat dilakukan untuk menghadapi munculnya strain parasit yangresisten terhadap artemisinin. Metode yang digunakan adalah studi kepustakaan. ResistensiP.falciparum terhadap obat-obat anti malaria disebabkan oleh perubahan spontan yangterjadi pada beberapa gen seperti P.falciparum multi drug resistance1 (Pfmdr1), P.falciparumchloroquine transporter (Pfcrt), P.falciparum dihydropteroate synthase (Pfdhps), P.falciparumdihydrofolate reductase (Pfdhfr), and P.falciparum multidrug resistance-associated proteins(Pfmrp). Penyebaran resistensi tersebut dipengaruhi oleh tingkat transmisi di sebuah wilayah.WHO telah menjalankan usaha untuk menanggulangi penyebaran resistensi tersebut misalnyadengan merekomendasikan penghentian monoterapi artemisinin, dan pemberian anti malariasetelah konfirmasi laboratorium. Selain itu, perlu adanya penggunaan obat kombinasi, produksirejimen dosis tetap, dan pengembangan obat anti malaria baru. Kesimpulan dari hasil studiini ialah munculnya malaria resisten terhadap artemisinin akan menghambat usaha eradikasimalaria karena itu diperlukan usaha-usaha untuk menanggulanginya.AbstractThe objective of this study was to describe the development of anti-malarial drug resistanceof the parasites and the efforts taken to contain the emergence of artemisinin resistant malaria.This was a literature study. The development of resistance to anti-malarial drugs are due tospontaneous changes in certain genes such as of P.falciparum multi drug resistance1 (Pfmdr1),P.falciparum chloroquine resistance transporter (Pfcrt), P.falciparum dihydropteroate synthase(Pfdhps), P.falciparum dihydrofolate reductase (Pfdhfr), and P.falciparum multidrug resistanceassociatedproteins (Pfmrp). The spread of the resistance depends on the transmission ratewithin each area. WHO has established a global plan to contain the spread of this resistance,such as recommendation to withdraw artemisinin-based monotherapies and administrationof treatment after laboratory confirmation. In addition, administration of anti-malarial drugcombination, production of fixed dose regimen and development of new drugs are necessary.The Conclusion is emergence of artemisinin resistant malaria will threaten malaria eradicationthus some efforts are necessarily needed to contain it.Afiliasi penulis: Bagian Parasitologi Fakultas Kedokteran Universitas Hasanudin
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Friedrich, M. J. "Resistance to Malaria Drugs." JAMA 305, no. 7 (February 16, 2011): 663. http://dx.doi.org/10.1001/jama.2011.134.
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Vale, Valdicley Vieira, Dayse Lúcia do Nascimento Brandão, Milena Cristina Martins Da Silva, Denise Bueno, Michael Dean Green, Sandro Percário, and Maria Fani Dolabela. "Malaria parasite resistance vicious cycle." Revista Eletrônica Acervo Saúde 11, no. 18 (December 18, 2019): e1708. http://dx.doi.org/10.25248/reas.e1708.2019.
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Objective: This paper analyzes the "vicious" cycle of malaria treatment as a consequence of restricted access to anti-malarial drugs. Literature review: Lack of public health policies in affected countries limits access to medicines. This leads patients to acquire drugs in "parallel" markets under the risk of quality deviations or falsified products. The use of these products can aggravate the disease, lead to death, and contribute to parasite resistance to drugs. There are reports of Plasmodium strains resistant to different antimalarial drugs, this creates the need to look for new therapeutic alternatives. These new drugs begin to be counterfeit or people use low quality drugs, selectung resistant strains again, making necessary further research to identify other therapeutic possibilities, restarting this vicious cycle. Final considerations: Therefore, it is important to create conditions for using good quality medicines supervised by health professionals, and ensure research of new alternatives, evaluating their activity on the parasite or the disease.
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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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Salomone, Salvatore, and Théophile Godfraind. "Drugs that reverse chloroquine resistance in malaria." Trends in Pharmacological Sciences 11, no. 11 (November 1990): 475–76. http://dx.doi.org/10.1016/0165-6147(90)90135-u.
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Rout, Usha K., A. S. Sanket, Brijesh S. Sisodia, Pradyumna K. Mohapatra, Sanghamitra Pati, Rajni Kant, and Gaurav R. Dwivedi. "A Comparative Review on Current and Future Drug Targets Against Bacteria & Malaria." Current Drug Targets 21, no. 8 (June 20, 2020): 736–75. http://dx.doi.org/10.2174/1389450121666200129103618.
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Long before the discovery of drugs like ‘antibiotic and anti-parasitic drugs’, the infectious diseases caused by pathogenic bacteria and parasites remain as one of the major causes of morbidity and mortality in developing and underdeveloped countries. The phenomenon by which the organism exerts resistance against two or more structurally unrelated drugs is called multidrug resistance (MDR) and its emergence has further complicated the treatment scenario of infectious diseases. Resistance towards the available set of treatment options and poor pipeline of novel drug development puts an alarming situation. A universal goal in the post-genomic era is to identify novel targets/drugs for various life-threatening diseases caused by such pathogens. This review is conceptualized in the backdrop of drug resistance in two major pathogens i.e. “Pseudomonas aeruginosa” and “Plasmodium falciparum”. In this review, the available targets and key mechanisms of resistance of these pathogens have been discussed in detail. An attempt has also been made to analyze the common drug targets of bacteria and malaria parasite to overcome the current drug resistance scenario. The solution is also hypothesized in terms of a present pipeline of drugs and efforts made by scientific community.
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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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Sharma, Vijay. "Therapeutic Drugs for Targeting Chloroquine Resistance in Malaria." Mini-Reviews in Medicinal Chemistry 5, no. 4 (April 1, 2005): 337–51. http://dx.doi.org/10.2174/1389557053544029.
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Singh, Gajinder Pal. "Dimension reduction of Malaria Box data allows efficient compound prioritization." F1000Research 5 (November 18, 2016): 2701. http://dx.doi.org/10.12688/f1000research.10121.1.
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Background: New anti-malarial drugs are needed to meet the challenge of artemisinin resistance and to achieve malaria elimination and eradication. The new anti-malarial compounds are expected to have many desirable properties, such as activity against multiple stages of Plasmodium, low host cytotoxicity, and low propensity for resistance development, but whether and how these properties might be linked to each other is not clear. A better understanding of the relationship between activities of compounds against different stages of Plasmodium could help in the development of strategies to prioritize compounds with maximum potential for further development. Methods: We utilized the large amount of data that has recently been generated on 400 anti-malarial Malaria Box compounds and performed statistical analyses, such as rank correlation, hierarchical clustering, and principal-component analyses, to test associations between activities against different stages of Plasmodium, other pathogens, and human cells. Results: We found significant positive correlations between the activities of compounds against different stages of Plasmodium. Our results also show toxicity associated with assays conducted at higher compound concentrations. Principal-component analyses (PCA) of the data allowed differentiation of Plasmodium-specific activity from general toxicity and predicted success in in vitro evolution of resistance. We found that a single principal-component can capture most of the desirable properties of Malaria Box compounds and can be used to rank compounds from most desirable to least desirable activity-profile. Conclusions: Here, we provide a systematic strategy to prioritize Malaria Box compounds for further development. This approach may be applied for prioritization of anti-malarial compounds in general.
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Peters, W. "The problem of drug resistance in malaria." Parasitology 90, no. 4 (April 1985): 705–15. http://dx.doi.org/10.1017/s003118200005232x.
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The resistance in human malaria is mainly of practical importance in relation to Plasmodium falciparum. Strains resistant not only to chloroquine but also to dihydrofolate reductase inhibitors, and even to potentiating combinations of these with sulphonamides or sulphones, are appearing in an ever increasing geographical area which now includes tropical Africa and India. Few new drugs are available or foreseen for the near future, mefloquine and artemisinine being the leading contenders. It is vital that all measures possible should be taken to protect such new compounds, their deployment in the form of judiciously selected combinations with other antimalarials being an essential procedure that should be followed. Drugs in new chemical classes and with different modes of action are still urgently needed. Reliance should not be placed on drugs alone to control malaria on a community basis.
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E, Hempelmann. "Plant-Derived Drugs in Malaria Treatment." Journal of Pharmaceutics and Therapeutics 4, no. 1 (June 10, 2018): 147–51. http://dx.doi.org/10.18314/jpt.v4i1.1188.
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Every year 880,000 people are killed by malaria, mostof them children in impoverished regions of the worldlacking adequate medical care. While many preventativemeasures, such as mosquito nets have decreased theincidence of malaria, once the disease is contracted,it must be treated. Many plasmodial species havedeveloped a frightening resistance to antimalarial agents,making the search for new, effective antimalarial agentsan urgent priority of global importance.
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Oku, Hiroyuki, Yu Hashimoto, Takashi Matsukawa, Kazuo Shinozuka, and Yuko Oku. "Novel Long Peptide Antigens Containing MHC Class I and Class II Binding Sequences Designed from Plasmodium falciparum Enolase." Advanced Engineering Forum 38 (November 2020): 63–68. http://dx.doi.org/10.4028/www.scientific.net/aef.38.63.
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Malaria caused by Plasmodium falciparum continues to be a major public health problem especially in tropical and sub-tropical regions of the world. Considering the growing resistance of parasites to anti-malarial drugs and of vector mosquitoes to insecticides, there is no doubt that the effective vaccine is the most awaiting tool to reduce the risk of malaria. Our synthetic studies have shown that a loop region (AD22 = 256ASEFYNSENKTYDLDFKTPNND277) of Plsmodium falciparum enolase has antigenic reactivity against patients’ sera and AD22 can produce inhibitory antibodies against in vitro parasite growth. In this paper, we will briefly present our ongoing research of malaria vaccine development and related model studies.
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Vandamme, Mieke, Kristel Van Laethem, and Erik De Clercq. "Managing Resistance to Anti-HIV Drugs." Drugs 57, no. 3 (1999): 337–61. http://dx.doi.org/10.2165/00003495-199957030-00006.
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Bousquet, Guilhem, and Anne Janin. "Reactive resistance to anti-angiogenic drugs." Aging 7, no. 5 (May 15, 2015): 282–83. http://dx.doi.org/10.18632/aging.100748.
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BOUCHER, C. "S133 Resistance to anti-retroviral drugs." Journal of the European Academy of Dermatology and Venereology 9 (September 1997): S32. http://dx.doi.org/10.1016/s0926-9959(97)90083-0.
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Giglione, Carmela, and Thierry Meinnel. "Resistance to anti-peptide deformylase drugs." Expert Opinion on Therapeutic Targets 5, no. 3 (June 2001): 415–18. http://dx.doi.org/10.1517/14728222.5.3.415.
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Kannigadu, Christina, and David D. N'Da. "Recent Advances in the Synthesis and Development of Nitroaromatics as Anti-Infective Drugs." Current Pharmaceutical Design 26, no. 36 (October 23, 2020): 4658–74. http://dx.doi.org/10.2174/1381612826666200331091853.
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: Infectious diseases commonly occur in tropical and sub-tropical countries. The pathogens of such diseases are able to multiply in human hosts, warranting their continual survival. Infections that are commonplace include malaria, chagas, trypanosomiasis, giardiasis, amoebiasis, toxoplasmosis and leishmaniasis. Malaria is known to cause symptoms, such as high fever, chills, nausea and vomiting, whereas chagas disease causes enlarged lymph glands, muscle pain, swelling and chest pain. People suffering from African trypanosomiasis may experience severe headaches, irritability, extreme fatigue and swollen lymph nodes. As an infectious disease progresses, the human host may also experience personality changes and neurologic problems. If left untreated, most of these diseases can lead to death. : Parasites, microbes and bacteria are increasingly adapting and generating strains that are resistant to current clinical drugs. Drug resistance creates an urgency for the development of new drugs to treat these infections. Nitro containing drugs, such as chloramphenicol, metronidazole, tinidazole and secnidazole had been banned for use as antiparasitic agents due to their toxicity. However, recent discoveries of nitrocontaining anti-tuberculosis drugs, i.e. delamanid and pretonamid, and the repurposing of flexinidazole for use in combination with eflornithine for the treatment of human trypanosomiasis, have ignited interest in nitroaromatic scaffolds as viable sources of potential anti-infective agents. : This review highlights the differences between old and new nitration methodologies. It furthermore offers insights into recent advances in the development of nitroaromatics as anti-infective drugs.
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Hajialiani, Fatemeh, Sedigheh Sadeghi, Delavar Shahbazzadeh, Fatemeh Tabatabaie, and Zahra Zamani. "Assessing Anti-malaria Effect of Naja Naja Oxiana Snake Venom by Real-time Polymerase Chain Reaction Method." Complementary Medicine Journal 11, no. 1 (April 1, 2021): 68–81. http://dx.doi.org/10.32598/cmja.11.1.1049.1.
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Objective: Malaria is one of the most important parasitic diseases and one of the important health issues especially in tropical and subtropical countries. The importance of this disease is due to its high prevalence and mortality, as well as drug resistance and side effects of common drugs used for its treatment. Snake venom is a complex mixture of active pharmaceutical ingredients. The present study aims to investigate the anti-Plasmodium falciparum activity of the purified fractions isolated from the venom of Iranian cobra snake (Naja Naja Oxiana) by real-time Polymerase Chain Reaction (PCR) method. The importance of this disease is due to its high prevalence, significant mortality, as well as drug resistance and, side effects of current drugs in treatment. Venom is a complex mixture of active pharmaceutical ingredients. The purpose of this study was to investigate the anti-Plasmodium falciparum activity of the purified fraction of Iranian cobra snake venom by Real -time PCR. Methods: After preparation and purification of lyophilized venom for determining the parasitic load, different fractions obtained from the venom of Naja Naja Oxiana put in different plates adjacent to Plasmodium falciparum (3D7) strain in the ring stage. The degree of parasitemia was determined by real-time PCR. Finally, the effective fraction with anti-malaria properties was identified. Results: The active fraction with a half maximal inhibitory concentration of 0.026 μg/mL was the most effective fraction on Plasmodium falciparum in vitro (P<0.001). Conclusion: The active fraction of Naja Naja Oxiana venom at the mentioned concentration has anti-malaria effect. This results can motivate the continuation of further research in this field.
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Guiguemde, W. Armand, Nicholas H. Hunt, Jintao Guo, Annael Marciano, Richard K. Haynes, Julie Clark, R. Kiplin Guy, and Jacob Golenser. "Treatment of Murine Cerebral Malaria by Artemisone in Combination with Conventional Antimalarial Drugs: Antiplasmodial Effects and Immune Responses." Antimicrobial Agents and Chemotherapy 58, no. 8 (June 9, 2014): 4745–54. http://dx.doi.org/10.1128/aac.01553-13.
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ABSTRACTThe decreasing effectiveness of antimalarial therapy due to drug resistance necessitates constant efforts to develop new drugs. Artemisinin derivatives are the most recent drugs that have been introduced and are considered the first line of treatment, but there are already indications ofPlasmodium falciparumresistance to artemisinins. Consequently, drug combinations are recommended for prevention of the induction of resistance. The research here demonstrates the effects of novel combinations of the new artemisinin derivative, artemisone, a recently described 10-alkylamino artemisinin derivative with improved antimalarial activity and reduced neurotoxicity. We here investigate its ability to killP. falciparumin a high-throughputin vitroassay and to protect mice against lethal cerebral malaria caused byPlasmodium bergheiANKA when used alone or in combination with established antimalarial drugs. Artemisone effects againstP. falciparumin vitrowere synergistic with halofantrine and mefloquine, and additive with 25 other drugs, including chloroquine and doxycycline. The concentrations of artemisone combinations that were toxic against THP-1 cellsin vitrowere much higher than their effective antimalarial concentration. Artemisone, mefloquine, chloroquine, or piperaquine given individually mostly protected mice against cerebral malaria caused byP. bergheiANKA but did not prevent parasite recrudescence. Combinations of artemisone with any of the other three drugs did completely cure most mice of malaria. The combination of artemisone and chloroquine decreased the ratio of proinflammatory (gamma interferon, tumor necrosis factor) to anti-inflammatory (interleukin 10 [IL-10], IL-4) cytokines in the plasma ofP. berghei-infected mice. Thus, artemisone in combinations with other antimalarial drugs might have a dual action, both killing parasites and limiting the potentially deleterious host inflammatory response.
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Ibraheem, Zaid O., R. Abd Majid, S. Mohd Noor, H. Mohd Sedik, and R. Basir. "Role of Different Pfcrt and Pfmdr-1 Mutations in Conferring Resistance to Antimalaria Drugs in Plasmodium falciparum." Malaria Research and Treatment 2014 (November 11, 2014): 1–17. http://dx.doi.org/10.1155/2014/950424.
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Emergence of drugs resistant strains of Plasmodium falciparum has augmented the scourge of malaria in endemic areas. Antimalaria drugs act on different intracellular targets. The majority of them interfere with digestive vacuoles (DVs) while others affect other organelles, namely, apicoplast and mitochondria. Prevention of drug accumulation or access into the target site is one of the mechanisms that plasmodium adopts to develop resistance. Plasmodia are endowed with series of transporters that shuffle drugs away from the target site, namely, pfmdr (Plasmodium falciparum multidrug resistance transporter) and pfcrt (Plasmodium falciparum chloroquine resistance transporter) which exist in DV membrane and are considered as putative markers of CQ resistance. They are homologues to human P-glycoproteins (P-gh or multidrug resistance system) and members of drug metabolite transporter (DMT) family, respectively. The former mediates drifting of xenobiotics towards the DV while the latter chucks them outside. Resistance to drugs whose target site of action is intravacuolar develops when the transporters expel them outside the DVs and vice versa for those whose target is extravacuolar. In this review, we are going to summarize the possible pfcrt and pfmdr mutation and their role in changing plasmodium sensitivity to different anti-Plasmodium drugs.
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Bray, Patrick G., and Stephen A. Ward. "Malaria chemotherapy: Resistance to quinoline containing drugs inPlasmodium falciparum." FEMS Microbiology Letters 113, no. 1 (October 1993): 1–7. http://dx.doi.org/10.1111/j.1574-6968.1993.tb06479.x.
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Kozlov, Max. "Resistance to front-line malaria drugs confirmed in Africa." Nature 597, no. 7878 (September 23, 2021): 604. http://dx.doi.org/10.1038/d41586-021-02592-6.
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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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Wicht, Kathryn J., Sachel Mok, and David A. Fidock. "Molecular Mechanisms of Drug Resistance in Plasmodium falciparum Malaria." Annual Review of Microbiology 74, no. 1 (September 8, 2020): 431–54. http://dx.doi.org/10.1146/annurev-micro-020518-115546.
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Understanding and controlling the spread of antimalarial resistance, particularly to artemisinin and its partner drugs, is a top priority. Plasmodium falciparum parasites resistant to chloroquine, amodiaquine, or piperaquine harbor mutations in the P. falciparum chloroquine resistance transporter (PfCRT), a transporter resident on the digestive vacuole membrane that in its variant forms can transport these weak-base 4-aminoquinoline drugs out of this acidic organelle, thus preventing these drugs from binding heme and inhibiting its detoxification. The structure of PfCRT, solved by cryogenic electron microscopy, shows mutations surrounding an electronegative central drug-binding cavity where they presumably interact with drugs and natural substrates to control transport. P. falciparum susceptibility to heme-binding antimalarials is also modulated by overexpression or mutations in the digestive vacuole membrane–bound ABC transporter PfMDR1 ( P. falciparum multidrug resistance 1 transporter). Artemisinin resistance is primarily mediated by mutations in P. falciparum Kelch13 protein (K13), a protein involved in multiple intracellular processes including endocytosis of hemoglobin, which is required for parasite growth and artemisinin activation. Combating drug-resistant malaria urgently requires the development of new antimalarial drugs with novel modes of action.
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Afaya, Agani, Solomon Mohammed Salia, Frederick Yaw Opare, Samira Ali, and Richard Adongo Afaya. "Patients’ adherence to antimalarial medication; self-report of patients at the Volta regional hospital of Ho, Ghana." International Journal of Research in Medical Sciences 5, no. 10 (September 28, 2017): 4234. http://dx.doi.org/10.18203/2320-6012.ijrms20174552.
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Background: Despite the advancement in malaria treatments and management; malaria morbidity and mortality is still on the increase. This phenomenon has been mostly attributed to the emergence and transmission resistance of the plasmodium parasite to drugs; which is as a result of non-adherence to anti-malaria medication. Therefore, the purpose of this study was to assess patients’ adherence to anti-malarial medications and the factors influencing their adherence in the Volta regional hospital.Methods: A descriptive cross-sectional study was employed. Convenience sampling technique was used in recruiting respondents. Data were collected within a period of 8 weeks from April to May 2017. Data were analyzed using descriptive statistics in the form of frequencies, percentages, mean and standard deviations which was generated by the use of IBM statistical package for social sciences version 23.Results: The average age of respondents surveyed for this study was 32.27±11.09 ranging from of 19 to 68 years. Majority (51.7%) of respondents were females and 76.7% of them being Christians. The study findings revealed that 36.6% of patient were completely adherent to anti-malarial medication. Over 90% of respondents agreed that the malarial medication had bad taste and it was an unpleasant feeling for them taking it.Conclusions: Poor adherence to antimalaria medications could play a role in the future development of drug resistance. As such, identifying ways to improve anti-malarial compliance will help mitigate drug resistance. Therefore, further studies should be carried out on ways to improve patients’ adherence to antimalarial medication.
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Sá, Juliana M., Jason L. Chong, and Thomas E. Wellems. "Malaria drug resistance: new observations and developments." Essays in Biochemistry 51 (October 24, 2011): 137–60. http://dx.doi.org/10.1042/bse0510137.
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Drug-resistant micro-organisms became widespread in the 20th Century, often with devastating consequences, in response to widespread use of natural and synthetic drugs against infectious diseases. Antimalarial resistance provides one of the earliest examples, following the introduction of new medicines that filled important needs for prophylaxis and treatment around the globe. In the present chapter, we offer a brief synopsis of major antimalarial developments from two natural remedies, the qinghaosu and cinchona bark infusions, and of synthetic drugs inspired by the active components of these remedies. We review some contributions that early efficacy studies of antimalarial treatment brought to clinical pharmacology, including convincing documentation of atebrine-resistant malaria in the 1940s, prior to the launching of what soon became first-choice antimalarials, chloroquine and amodiaquine. Finally, we discuss some new observations on the molecular genetics of drug resistance, including delayed parasite clearances that have been increasingly observed in response to artemisinin derivatives in regions of South-East Asia.
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Kesely, Kristina, Panae Noomuna, Michal Vieth, Philip Hipskind, Kasturi Haldar, Antonella Pantaleo, Francesco Turrini, and Philip S. Low. "Identification of tyrosine kinase inhibitors that halt Plasmodium falciparum parasitemia." PLOS ONE 15, no. 11 (November 12, 2020): e0242372. http://dx.doi.org/10.1371/journal.pone.0242372.
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Although current malaria therapies inhibit pathways encoded in the parasite’s genome, we have looked for anti-malaria drugs that can target an erythrocyte component because development of drug resistance might be suppressed if the parasite cannot mutate the drug’s target. In search for such erythrocyte targets, we noted that human erythrocytes express tyrosine kinases, whereas the Plasmodium falciparum genome encodes no obvious tyrosine kinases. We therefore screened a library of tyrosine kinase inhibitors from Eli Lilly and Co. in a search for inhibitors with possible antimalarial activity. We report that although most tyrosine kinase inhibitors exerted no effect on parasite survival, a subset of tyrosine kinase inhibitors displayed potent anti-malarial activity. Moreover, all inhibitors found to block tyrosine phosphorylation of band 3 specifically suppressed P. falciparum survival at the parasite egress stage of its intra-erythrocyte life cycle. Conversely, tyrosine kinase inhibitors that failed to block band 3 tyrosine phosphorylation but still terminated the parasitemia were observed to halt parasite proliferation at other stages of the parasite’s life cycle. Taken together these results suggest that certain erythrocyte tyrosine kinases may be important to P. falciparum maturation and that inhibitors that block these kinases may contribute to novel therapies for P. falciparum malaria.
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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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Alvarez, Jesus R., Abdulla Al-Khan, and Joseph J. Apuzzio. "Malaria in Pregnancy." Infectious Diseases in Obstetrics and Gynecology 13, no. 4 (2005): 229–36. http://dx.doi.org/10.1155/2005/768392.
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Recently, there has been a resurgence of malaria in densely populated areas of the United States secondary to human migration from endemic areas where factors such as cessation of vector control, vector resistance to insecticides, disease resistance to drugs, environmental changes, political instability, and indifference, have played a role for malaria becoming an overwhelming infection of these tropical underdeveloped countries. It is important for health care providers of gravida to be alert of the disease and its effects on pregnancy.
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Capper, Michael, Paul O'Neill, Giancarlo Biagini, Samar Hasnain, and Svetlana Antonyuk. "Overcoming drug-resistant malaria through rational drug design in cytochrome bc1." Acta Crystallographica Section A Foundations and Advances 70, a1 (August 5, 2014): C806. http://dx.doi.org/10.1107/s2053273314091931.
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Over three billion people live in regions affected by malaria and there are over one million deaths each year [1]. Malaria is caused by the Plasmodium parasite and various drugs are currently used in both treatment and prophylaxis but resistant strains are rapidly emerging. One of the most commonly used anti-malarial drugs is Atovaquone, a hydroxynapthoquinone that is currently used in combination with Proguanil and sold as Malarone™. Atovaquone targets cytochrome bc1 (Complex III, ubiquinol-cytochrome c oxidoreductase), a multi subunit electron transfer protein complex embedded in the inner mitochondrial membrane [2]. Drug resistance rises through a single point mutation in cytochrome b at the Qo site, one of two quinone binding sites. By visualising compounds bound to cytochrome bc1 through x-ray crystallography, it may be possible to modify the compounds to both bind stronger and more specifically. We have worked on compounds that recently failed phase I clinical trials due to cross-reactivity with human cytochrome bc1 [3]. Our structural studies have shown that these compounds appear to bind at the Qi site, which would overcome current drug-resistant strains. Further work here could produce a novel class of anti-malarial drug.
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Abdulkareem, Adam O., Abdulkareem O. Babamale, Lucky O. Owolusi, Simbiat A. Busari, and Lawrence A. Olatunji. "Anti-plasmodial activity of sodium acetate in Plasmodium berghei-infected mice." Journal of Basic and Clinical Physiology and Pharmacology 29, no. 5 (September 25, 2018): 493–98. http://dx.doi.org/10.1515/jbcpp-2017-0203.
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Abstract Background Continuous increase in drug resistance has hindered the control of malaria infection and resulted in multi-drug-resistant parasite strains. This, therefore, intensifies the search for alternative treatments with no or less side effects. Several histone deacetylase inhibitors have been characterised to possess anti-malaria activity; however, their further development as anti-malaria agents has not recorded much success. The present study investigated the anti-plasmodial activity of sodium acetate in Plasmodium berghei-infected mice, aiming at finding a better alternative source of malaria chemotherapy. Methods Thirty female Swiss albino mice were randomly distributed into six groups. Groups A (uninfected control) and B (infected control) received only distilled water. Group C (artesunate control) were infected and treated orally with 4 mg/kg artesunate on the first day, and subsequently 2 mg/kg artesunate. Groups D, E and F were infected and orally treated with 50, 100 and 200 mg/kg sodium acetate, respectively. Results Sodium acetate significantly lowered parasitaemia (p<0.05) after 4 days post-treatment, and the parasite inhibition rate of 68.5% at 50 mg/kg compared favourably with the 73.3% rate of artesunate. Similarly, administration of 50 mg/kg sodium acetate improved serum total cholesterol relatively better than artesunate. Our results also revealed that sodium acetate does not interfere with liver function, as there was no significant difference (p>0.05) in the serum activities of aspartate aminotransferase and alanine aminotransferase in both infected treated and uninfected mice. Conclusions This study shows that sodium acetate may be a safe alternative source of anti-malaria drugs. Its effect on the serum total cholesterol also predicts its ability in correcting malaria-induced metabolic syndromes.
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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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Kunkel, Amber, Michael White, and Patrice Piola. "Novel anti-malarial drug strategies to prevent artemisinin partner drug resistance: A model-based analysis." PLOS Computational Biology 17, no. 3 (March 25, 2021): e1008850. http://dx.doi.org/10.1371/journal.pcbi.1008850.
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Emergence of resistance to artemisinin and partner drugs in the Greater Mekong Subregion has made elimination of malaria from this region a global priority; it also complicates its achievement. Novel drug strategies such as triple artemisinin combination therapies (ACTs) and chemoprophylaxis have been proposed to help limit resistance and accelerate elimination. The objective of this study was to better understand the potential impacts of triple ACTs and chemoprophylaxis, using a mathematical model parameterized using data from Cambodia. We used a simple compartmental model to predict trends in malaria incidence and resistance in Cambodia from 2020–2025 assuming no changes in transmission since 2018. We assessed three scenarios: a status quo scenario with artesunate-mefloquine (ASMQ) as treatment; a triple ACT scenario with dihydroartemisinin-piperaquine (DP) plus mefloquine (MQ) as treatment; and a chemoprophylaxis scenario with ASMQ as treatment plus DP as chemoprophylaxis. We predicted MQ resistance to increase under the status quo scenario. Triple ACT treatment reversed the spread of MQ resistance, but had no impact on overall malaria incidence. Joint MQ-PPQ resistance declined under the status quo scenario for the baseline parameter set and most sensitivity analyses. Compared to the status quo, triple ACT treatment limited spread of MQ resistance but also slowed declines in PPQ resistance in some sensitivity analyses. The chemoprophylaxis scenario decreased malaria incidence, but increased the spread of strains resistant to both MQ and PPQ; both effects began to reverse after the intervention was removed. We conclude that triple ACTs may limit spread of MQ resistance in the Cambodia, but would have limited impact on malaria incidence and might slow declines in PPQ resistance. Chemoprophylaxis could have greater impact on incidence but also carries higher risks of resistance. Aggressive strategies to limit transmission the GMS are needed to achieve elimination goals, but any intervention should be accompanied by monitoring for drug resistance.
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van Schalkwyk, Donelly A., and Colin J. Sutherland. "Malaria resistance to non-artemisinin partner drugs: how to reACT." Lancet Infectious Diseases 15, no. 6 (June 2015): 621–23. http://dx.doi.org/10.1016/s1473-3099(15)70080-0.
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Janssen, M. A., and W. J. M. Martens. "Modeling Malaria as a Complex Adaptive System." Artificial Life 3, no. 3 (July 1997): 213–36. http://dx.doi.org/10.1162/artl.1997.3.3.213.
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As the resistance of the malaria parasite to antimalarial drugs continues to increase, as does that of the malarial mosquito to insecticides, the efficacy of efforts to control malaria in many tropical countries is diminishing. This trend, together with the projected consequences of climate change, may prove to exacerbate substantially the significance of malaria in the coming decades. In this article we introduce the use of an evolutionary modeling approach to simulate the adaptation of mosquitoes and parasites to the available pesticides and drugs. By coupling genetic algorithms with a dynamic malaria-epidemiological model, we derive a complex adaptive system capable of simulating adapting and evolving processes within both the mosquito and the parasite populations. This approach is used to analyze malaria management strategies appropriate to regions of higher and lower degrees of endemicity. The results suggest that adequate use of insecticides and drugs may reduce the occurrence of malaria in regions of low endemicity, although increased efforts would be necessary in the event of a climate change. However, our model indicates that in regions of high endemicity the use of insecticides and drugs may lead to an increase in incidence due to enhanced resistance development. Projected climate change, on the other hand, may lead to a limited reduction of the occurrence of malaria due to the presence of a higher percentage of immune persons in the older age class.
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Amelo, Wote, and Eyasu Makonnen. "Efforts Made to Eliminate Drug-Resistant Malaria and Its Challenges." BioMed Research International 2021 (August 30, 2021): 1–12. http://dx.doi.org/10.1155/2021/5539544.
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Since 2000, a good deal of progress has been made in malaria control. However, there is still an unacceptably high burden of the disease and numerous challenges limiting advancement towards its elimination and ultimate eradication. Among the challenges is the antimalarial drug resistance, which has been documented for almost all antimalarial drugs in current use. As a result, the malaria research community is working on the modification of existing treatments as well as the discovery and development of new drugs to counter the resistance challenges. To this effect, many products are in the pipeline and expected to be marketed soon. In addition to drug and vaccine development, mass drug administration (MDA) is under scientific scrutiny as an important strategy for effective utilization of the developed products. This review discusses the challenges related to malaria elimination, ongoing approaches to tackle the impact of drug-resistant malaria, and upcoming antimalarial drugs.
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Baird, J. Kevin. "Resistance to Therapies for Infection by Plasmodium vivax." Clinical Microbiology Reviews 22, no. 3 (July 2009): 508–34. http://dx.doi.org/10.1128/cmr.00008-09.
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SUMMARY The gravity of the threat posed by vivax malaria to public health has been poorly appreciated. The widely held misperception of Plasmodium vivax as being relatively infrequent, benign, and easily treated explains its nearly complete neglect across the range of biological and clinical research. Recent evidence suggests a far higher and more-severe disease burden imposed by increasingly drug-resistant parasites. The two frontline therapies against vivax malaria, chloroquine and primaquine, may be failing. Despite 60 years of nearly continuous use of these drugs, their respective mechanisms of activity, resistance, and toxicity remain unknown. Although standardized means of assessing therapeutic efficacy against blood and liver stages have not been developed, this review examines the provisional in vivo, ex vivo, and animal model systems for doing so. The rationale, design, and interpretation of clinical trials of therapies for vivax malaria are discussed in the context of the nuance and ambiguity imposed by the hypnozoite. Fielding new drug therapies against real-world vivax malaria may require a reworking of the strategic framework of drug development, namely, the conception, testing, and evaluation of sets of drugs designed for the cure of both blood and liver asexual stages as well as the sexual blood stages within a single therapeutic regimen.
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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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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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Nsanzabana, Christian. "Resistance to Artemisinin Combination Therapies (ACTs): Do Not Forget the Partner Drug!" Tropical Medicine and Infectious Disease 4, no. 1 (February 1, 2019): 26. http://dx.doi.org/10.3390/tropicalmed4010026.
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Artemisinin-based combination therapies (ACTs) have become the mainstay for malaria treatment in almost all malaria endemic settings. Artemisinin derivatives are highly potent and fast acting antimalarials; but they have a short half-life and need to be combined with partner drugs with a longer half-life to clear the remaining parasites after a standard 3-day ACT regimen. When introduced, ACTs were highly efficacious and contributed to the steep decrease of malaria over the last decades. However, parasites with decreased susceptibility to artemisinins have emerged in the Greater Mekong Subregion (GMS), followed by ACTs’ failure, due to both decreased susceptibility to artemisinin and partner drug resistance. Therefore, there is an urgent need to strengthen and expand current resistance surveillance systems beyond the GMS to track the emergence or spread of artemisinin resistance. Great attention has been paid to the spread of artemisinin resistance over the last five years, since molecular markers of decreased susceptibility to artemisinin in the GMS have been discovered. However, resistance to partner drugs is critical, as ACTs can still be effective against parasites with decreased susceptibility to artemisinins, when the latter are combined with a highly efficacious partner drug. This review outlines the different mechanisms of resistance and molecular markers associated with resistance to partner drugs for the currently used ACTs. Strategies to improve surveillance and potential solutions to extend the useful therapeutic lifespan of the currently available malaria medicines are proposed.
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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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Singh, Gajinder Pal. "Conservation of gene essentiality in Apicomplexa and its application for prioritization of anti-malarial drug targets." F1000Research 6 (January 9, 2017): 23. http://dx.doi.org/10.12688/f1000research.10559.1.
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New anti-malarial drugs are needed to address the challenge of artemisinin resistance and to achieve malaria elimination and eradication. Target-based screening of inhibitors is a major approach for drug discovery, but its application to malaria has been limited by the availability of few validated drug targets in Plasmodium. Here we utilize the recently available large-scale gene essentiality data in Plasmodium berghei and a related apicomplexan pathogen, Toxoplasma gondii, to identify potential anti-malarial drug targets. We find significant conservation of gene essentiality in the two apicomplexan parasites. The conservation of essentiality could be used to prioritize enzymes that are essential across the two parasites and show no or low sequence similarity to human proteins. Novel essential genes in Plasmodium could be predicted based on their essentiality in T. gondii. Essential genes in Plasmodium showed higher expression, evolutionary conservation and association with specific functional classes. We expect that the availability of a large number of novel potential drug targets would significantly accelerate anti-malarial drug discovery.
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Tang, Yu-Qing, Qian Ye, He Huang, and Wei-Yi Zheng. "An Overview of Available Antimalarials: Discovery, Mode of Action and Drug Resistance." Current Molecular Medicine 20, no. 8 (December 29, 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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Mundell, Ian. "Can resistance to anti-HIV drugs be advantageous?" Inpharma Weekly &NA;, no. 891 (June 1993): 5. http://dx.doi.org/10.2165/00128413-199308910-00009.
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Pannu, Ashok K. "Malaria today: advances in management and control." Tropical Doctor 49, no. 3 (May 6, 2019): 160–64. http://dx.doi.org/10.1177/0049475519846382.
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Over the past two decades, malaria-related deaths have reduced substantially, especially in African children. However, the global malaria burden still remains high. The recent emergence of resistance to artemisinin, the backbone of malaria management, could threaten malaria control. Importantly, over the past five years, there has been an upsurge in research in the development of novel antimalarial drugs (and combinations), malaria vaccine and new vector-control strategies that can boost the malaria control programme.
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MARIJANI, THERESIA, and EDWARD LUNGU. "A WITHIN HOST MODEL OF BLOOD STAGE MALARIA WITH TREATMENT." Journal of Biological Systems 25, no. 01 (March 2017): 1–27. http://dx.doi.org/10.1142/s0218339017500012.
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We consider a mathematical model for malaria involving, susceptible red blood cells (RBCs), latent infected red blood cells (RBCs), active IRBCs, intracellular parasites, extracellular parasites and effector cells. We extend the model to include effect of treatment on the prognosis of malaria. One of the questions addressed in our study is: what range of the parameter, [Formula: see text] which denotes the number of intracellular parasites released from a naturally dying activated infected red blood cell can lead to malaria pathogenesis? Sensitivity analysis revealed that poor parametric estimation can lead to wrong disease prognosis, and consequently to over or under-prescription of treatment drugs. In malaria endemic areas where the parasite is developing resistance to the drugs, this can limit options of treatment drugs. We recommend that the administration of malaria treatment drugs should be done under supervision as is the case for TB to ensure complete adherence to treatment and reduce the emergence of malaria drug resistant strains. Secondly, we recommend that individuals with malaria or showing symptoms of the disease should be tested for other chronic infections which could complicate the treatment of malaria.
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Azlin, Emil, Ichwan HH Batubara, Wisman Dalimunte, Charles Siregar, Bidasari Lubis, Munar Lubis, and Syahril Pasaribu. "The effectiveness of chloroquine compared to Fansidar in treating falciparum malaria." Paediatrica Indonesiana 44, no. 1 (October 10, 2016): 17. http://dx.doi.org/10.14238/pi44.1.2004.17-20.
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Background The most difficult problem in eradicating malaria isthe resistance of P. falciparum to drugs. Mandailing Natal has thehighest malaria incidence in North Sumatera.Objective This study aimed to investigate the efficacy of chloro-quine and Fansidar in treating falciparum malaria.Methods A randomized double-blind study was done from April toMay 2001. Eighty-three patients with acute uncomplicated P.falciparum malaria infection were randomized into two groups.Group I (35 patients) received chloroquine and group II (48 pa-tients) received Fansidar. Blood examinations were performed onthe 1 st , 2 nd , 7 th , and 28 th days.Results The resistance of P. falciparum to drugs in the chloro-quine group were found in 10 patients with R II and 1 patients withR III, while in the Fansidar group, there were 14 patients with R II.Conclusion The efficacy of chloroquine and Fansidar in treatingfalciparum malaria was not significantly different
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Summers, Kelly L. "A Structural Chemistry Perspective on the Antimalarial Properties of Thiosemicarbazone Metal Complexes." Mini-Reviews in Medicinal Chemistry 19, no. 7 (March 28, 2019): 569–90. http://dx.doi.org/10.2174/1389557518666181015152657.
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Malaria is a potentially life-threatening disease, affecting approx. 214 million people worldwide. Malaria is caused by a protozoan, Plasmodium falciparum, which is transmitted through the Anopheles mosquito. Malaria treatment is becoming more challenging due to rising resistance against the antimalarial drug, chloroquine. Novel compounds that target aspects of parasite development are being explored in attempts to overcome this wide-spread problem. Anti-malarial drugs target specific aspects of parasite growth and development within the human host. One of the most effective targets is the inhibition of hematin formation, either through inhibition of cysteine proteases or through iron chelation. Metal-thiosemicarbazone (TSC) complexes have been tested for antimalarial efficacy against drug-sensitive and drug-resistant strains of P. falciparum. An array of TSC complexes with numerous transition metals, including ruthenium, palladium, and gold has displayed antiplasmodial activity. Au(I)- and Pd(II)-TSC complexes displayed the greatest potency; 4-amino-7-chloroquine moieties were also found to improve antiplasmodial activity of TSCs. Although promising metal-TSC drug candidates have been tested against laboratory strains of P. falciparum, problems arise when attempting to compare between studies. Future work should strive to completely characterize synthesized metal-TSC structures and assess antiplasmodial potency against several drug-sensitive and drugresistant strains. Future studies need to precisely determine IC50 values for antimalarial drugs, chloroquine and ferroquine, to establish accurate standard values. This will make future comparisons across studies more feasible and potentially help reveal structure-function relationships. Investigations that attempt to link drug structures or properties to antiplasmodial mechanism(s) of action will aid in the design of antimalarial drugs that may combat rising drug resistance.
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de Koning, Harry P. "Drug resistance in protozoan parasites." Emerging Topics in Life Sciences 1, no. 6 (December 22, 2017): 627–32. http://dx.doi.org/10.1042/etls20170113.
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As with all other anti-infectives (antibiotics, anti-viral drugs, and anthelminthics), the limited arsenal of anti-protozoal drugs is being depleted by a combination of two factors: increasing drug resistance and the failure to replace old and often shamefully inadequate drugs, including those compromised by (cross)-resistance, through the development of new anti-parasitics. Both factors are equally to blame: a leaking bathtub may have plenty of water if the tap is left open; if not, it will soon be empty. Here, I will reflect on the factors that contribute to the drug resistance emergency that is unfolding around us, specifically resistance in protozoan parasites.
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Afonso, A., P. Hunt, S. Cheesman, A. C. Alves, C. V. Cunha, V. do Rosário, and P. Cravo. "Malaria Parasites Can Develop Stable Resistance to Artemisinin but Lack Mutations in Candidate Genes atp6 (Encoding the Sarcoplasmic and Endoplasmic Reticulum Ca2+ ATPase), tctp, mdr1, and cg10." Antimicrobial Agents and Chemotherapy 50, no. 2 (February 2006): 480–89. http://dx.doi.org/10.1128/aac.50.2.480-489.2006.
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ABSTRACT Resistance of Plasmodium falciparum to drugs such as chloroquine and sulfadoxine-pyrimethamine is a major problem in malaria control. Artemisinin (ART) derivatives, particularly in combination with other drugs, are thus increasingly used to treat malaria, reducing the probability that parasites resistant to the components will emerge. Although stable resistance to artemisinin has yet to be reported from laboratory or field studies, its emergence would be disastrous because of the lack of alternative treatments. Here, we report for the first time, to our knowledge, genetically stable and transmissible ART and artesunate (ATN)-resistant malaria parasites. Each of two lines of the rodent malaria parasite Plosmodium chabaudi chabaudi, grown in the presence of increasing concentrations of ART or ATN, showed 15-fold and 6-fold increased resistance to ART and ATN, respectively. Resistance remained stable after cloning, freeze-thawing, after passage in the absence of drug, and transmission through mosquitoes. The nucleotide sequences of the possible genetic modulators of ART resistance (mdr1, cg10, tctp, and atp6) of sensitive and resistant parasites were compared. No mutations in these genes were identified. In addition we investigated whether changes in the copy number of these genes could account for resistance but found that resistant parasites retained the same number of copies as their sensitive progenitors. We believe that this is the first report of a malaria parasite with genetically stable and transmissible resistance to artemisinin or its derivatives.