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Malaria drug resistance

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https://www.readbyqxmd.com/read/28333961/phytochemical-investigation-of-aloe-pulcherrima-roots-and-evaluation-for-its-antibacterial-and-antiplasmodial-activities
#1
Dele Abdissa, Girma Geleta, Ketema Bacha, Negera Abdissa
Medicinal plants with documented traditional uses remain an important source for the treatment of a wide range of ailments. Evidence shows that majority of the Ethiopian population are still dependent on traditional medicine. Aloe pulcherrima Gilbert & Sebsebe is one of the endemic Aloe species traditionally used for the treatment of malaria and wound healing in central, Southern and Northern part of Ethiopia. The aim of the current study was, therefore, to isolate active compounds from roots of A. pulcherrima and evaluate for their antibacterial and antiplasmodial activities using standard test strains...
2017: PloS One
https://www.readbyqxmd.com/read/28333921/bioenergetics-based-modeling-of-plasmodium-falciparum-metabolism-reveals-its-essential-genes-nutritional-requirements-and-thermodynamic-bottlenecks
#2
Anush Chiappino-Pepe, Stepan Tymoshenko, Meriç Ataman, Dominique Soldati-Favre, Vassily Hatzimanikatis
Novel antimalarial therapies are urgently needed for the fight against drug-resistant parasites. The metabolism of malaria parasites in infected cells is an attractive source of drug targets but is rather complex. Computational methods can handle this complexity and allow integrative analyses of cell metabolism. In this study, we present a genome-scale metabolic model (iPfa) of the deadliest malaria parasite, Plasmodium falciparum, and its thermodynamics-based flux analysis (TFA). Using previous absolute concentration data of the intraerythrocytic parasite, we applied TFA to iPfa and predicted up to 63 essential genes and 26 essential pairs of genes...
March 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28327793/insights-into-cytochrome-bc1-complex-binding-mode-of-antimalarial-2-hydroxy-1-4-naphthoquinones-through-molecular-modelling
#3
Ana Carolina Rennó Sodero, Bárbara Abrahim-Vieira, Pedro Henrique Monteiro Torres, Pedro Geraldo Pascutti, Célia Rs Garcia, Vitor Francisco Ferreira, David Rodrigues da Rocha, Sabrina Baptista Ferreira, Floriano Paes Silva
BACKGROUND: Malaria persists as a major public health problem. Atovaquone is a drug that inhibits the respiratory chain of Plasmodium falciparum, but with serious limitations like known resistance, low bioavailability and high plasma protein binding. OBJECTIVES: The aim of this work was to perform molecular modelling studies of 2-hydroxy-1,4-naphthoquinones analogues of atovaquone on the Qo site of P. falciparum cytochrome bc1 complex (Pfbc1) to suggest structural modifications that could improve their antimalarial activity...
April 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28327148/drug-resistance-mediating-plasmodium-falciparum-polymorphisms-and-clinical-presentations-of-parasitaemic-children-in-uganda
#4
Stephen Tukwasibwe, Patrick Tumwebaze, Melissa Conrad, Emmanuel Arinaitwe, Moses R Kamya, Grant Dorsey, Samuel L Nsobya, Bryan Greenhouse, Philip J Rosenthal
BACKGROUND: Plasmodium falciparum genetic polymorphisms that mediate altered drug sensitivity may impact upon virulence. In a cross-sectional study, Ugandan children with infections mutant at pfcrt K76T, pfmdr1 N86Y, or pfmdr1 D1246Y had about one-fourth the odds of symptomatic malaria compared to those with infections with wild type (WT) sequences. However, results may have been confounded by greater likelihood in those with symptomatic disease of higher density mixed infections and/or recent prior treatment that selected for WT alleles...
March 21, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28327043/handwashing
#5
Erin Dean
Essential facts Antimicrobial resistance develops when medicines are used inappropriately. Global estimates suggest that every year more than 700,000 people die from drug-resistant strains of common bacterial and viral infections, such as tuberculosis, malaria and HIV. If antimicrobial resistance continues to increase, this number could rise to 10 million a year by 2050.
March 22, 2017: Nursing Standard
https://www.readbyqxmd.com/read/28323886/contribution-of-urinary-tract-infection-to-the-burden-of-febrile-illnesses-in-young-children-in-rural-kenya
#6
Wechuli Geoffrey Masika, Wendy Prudhomme O'Meara, Thomas L Holland, Janice Armstrong
INTRODUCTION: The clinical features of UTI in young children may not localize to the urinary tract and closely resemble other febrile illnesses. In malaria endemic areas, a child presenting with fever is often treated presumptively for malaria without investigation for UTI. Delayed or inadequate treatment of UTI increases the risk of bacteremia and renal scarring in young children and subsequently complications as hypertension and end stage renal disease in adulthood. METHODS: A cross-sectional study was carried out in a hospital in western Kenya...
2017: PloS One
https://www.readbyqxmd.com/read/28303837/prevalence-of-multiple-drug-resistant-plasmodium-falciparum-malaria-cases-in-northeast-india
#7
Jitendra Sharma, Siraj Ahmed Khan, Monika Soni, Prafulla Dutta
Two numbers of Plasmodium falciparum field isolates from Gossingpara, Runikhata area in Chirang district of Assam had shown multiple mutations in Pfcrt-dhfr-dhps gene (up to seven mutations: One mutation in Pfcrt gene, three mutations in Pfdhfr gene and three mutations in Pfdhps gene). Similarly, two cases in Bat camp, Miao area under Changlang district of Arunachal Pradesh had shown a total of eight mutations, of which one mutation in Pfcrt gene, three mutations in Pfdhfr gene, three mutations in Pfdhps gene and one mutation in PfATPase6 gene...
January 2017: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28302108/confirmation-of-plasmodium-falciparum-in-vitro-resistance-to-monodesethylamodiaquine-and-chloroquine-in-dakar-senegal-in-2015
#8
Silman Diawara, Marylin Madamet, Mame Bou Kounta, Gora Lo, Khalifa Ababacar Wade, Aminata Nakoulima, Raymond Bercion, Rémy Amalvict, Mamadou Wague Gueye, Bécaye Fall, Bakary Diatta, Bruno Pradines
BACKGROUND: In response to increasing resistance to anti-malarial drugs, Senegal adopted artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria in 2006. However, resistance of Plasmodium falciparum parasites to artemisinin derivatives, characterized by delayed parasite clearance after treatment with ACT or artesunate monotherapy, has recently emerged and rapidly spread in Southeast Asia. After 10 years of stability with rates ranging from 5.6 to 11...
March 16, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28302017/targeting-pyrimidine-pathway-of-plasmodium-knowlesi-new-strategies-towards-identification-of-novel-antimalarial-chemotherapeutic-agents
#9
Mayank Rashmi, Manoj Kumar Yadav, D Swati
Plasmodium knowlesi has been recently recognized as a human malarial parasite, particularly in the region of south-east Asia. The effective prevention and treatment of this disease is increasingly bound to fail due to the emergence of drug resistance. Hence, design of new drugs against known targets is gaining importance. Pyrimidine pathway is a crucial metabolic pathway in P. knowlesi, and the enzymes involved are also unique in terms of their structure and function as compared to its human counterpart. Thus targeting Dihydroorotase, an enzyme involved in the pyrimidine pathway, provides a promising route for novel drug development...
March 15, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28300558/therapeutic-efficacy-of-chloroquine-for-the-treatment-of-plasmodium-vivax-malaria-among-outpatients-at-shawa-robit-health-care-center-north-east-ethiopia
#10
Seble Seifu, Ahmed Zeynudin, Endalew Zemene, Sultan Suleman, Abdissa Biruksew
Nearly 40% of all malaria infection in Ethiopia is caused by Plasmodium vivax (P. vivax). Chloroquine (CQ) is the first line treatment for confirmed P. vivax malaria in the country. However, the efficacy of this drug has been compromised by CQ resistant P. vivax (CRPv) strains. Therefore, the present study was aimed at assessing the therapeutic efficacy of CQ for treatment of P. vivax malaria at Shawa Robit Health Care Centre, North-Ease Ethiopia. A one-arm, 28-day follow-up, in vivo therapeutic efficacy study was conducted from October 2013 to February 2014...
March 11, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28298235/clinical-and-molecular-surveillance-of-drug-resistant-vivax-malaria-in-myanmar-2009-2016
#11
Myat Htut Nyunt, Jin-Hee Han, Bo Wang, Khin Myo Aye, Kyin Hla Aye, Seong-Kyun Lee, Ye Htut, Myat Phone Kyaw, Kay Thwe Han, Eun-Taek Han
BACKGROUND: One of the major challenges for control and elimination of malaria is ongoing spread and emergence of drug resistance. While epidemiology and surveillance of the drug resistance in falciparum malaria is being explored globally, there are few studies on drug resistance vivax malaria. METHODS: To assess the spread of drug-resistant vivax malaria in Myanmar, a multisite, prospective, longitudinal study with retrospective analysis of previous therapeutic efficacy studies, was conducted...
March 16, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28289248/antimalarial-drug-resistance-a-threat-to-malaria-elimination
#12
Didier Menard, Arjen Dondorp
Increasing antimalarial drug resistance once again threatens effective antimalarial drug treatment, malaria control, and elimination. Artemisinin combination therapies (ACTs) are first-line treatment for uncomplicated falciparum malaria in all endemic countries, yet partial resistance to artemisinins has emerged in the Greater Mekong Subregion. Concomitant emergence of partner drug resistance is now causing high ACT treatment failure rates in several areas. Genetic markers for artemisinin resistance and several of the partner drugs have been established, greatly facilitating surveillance...
March 13, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28289193/host-immunity-to-plasmodium-falciparum-and-the-assessment-of-emerging-artemisinin-resistance-in-a-multinational-cohort
#13
Ricardo Ataide, Elizabeth A Ashley, Rosanna Powell, Jo-Anne Chan, Michael J Malloy, Katherine O'Flaherty, Eizo Takashima, Christine Langer, Takafumi Tsuboi, Arjen M Dondorp, Nicholas P Day, Mehul Dhorda, Rick M Fairhurst, Pharath Lim, Chanaki Amaratunga, Sasithon Pukrittayakamee, Tran Tinh Hien, Ye Htut, Mayfong Mayxay, M Abul Faiz, James G Beeson, Francois Nosten, Julie A Simpson, Nicholas J White, Freya J I Fowkes
Artemisinin-resistant falciparum malaria, defined by a slow-clearance phenotype and the presence of kelch13 mutants, has emerged in the Greater Mekong Subregion. Naturally acquired immunity to malaria clears parasites independent of antimalarial drugs. We hypothesized that between- and within-population variations in host immunity influence parasite clearance after artemisinin treatment and the interpretation of emerging artemisinin resistance. Antibodies specific to 12 Plasmodium falciparum sporozoite and blood-stage antigens were determined in 959 patients (from 11 sites in Southeast Asia) participating in a multinational cohort study assessing parasite clearance half-life (PCt1/2) after artesunate treatment and kelch13 mutations...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28289029/antimalarial-hybrid-molecules-a-close-reality-or-a-distant-dream
#14
Drishti Agarwal, Rinkoo D Gupta, Satish K Awasthi
Emergence of drug resistant Plasmodium falciparum strains has led to a situation of haste in the scientific and pharmaceutical communities. Hence, all their efforts are redirected towards finding alternate chemotherapeutic agents that are capable of combating multi-drug resistant parasite strains. In the above light, scientists have come up with the concept of hybridisation of two or more active pharmacophores into a single chemical entity, resulting in 'antimalarial hybrids.' The approach has been applied widely for lead generation against deadly diseases such as cancer and AIDS, with proven potential to be used as novel drugs, but is comparatively new in the sphere of antimalarial drug discovery...
March 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28289025/age-weight-and-cyp2d6-genotype-are-major-determinants-of-primaquine-pharmacokinetics-in-african-children
#15
Bronner P Gonçalves, Helmi Pett, Alfred B Tiono, Daryl Murry, Sodiomon Sirima, Mikko Niemi, Teun Bousema, Chris Drakeley, Rob Ter Heine
Low dose primaquine is recommended to prevent Plasmodium falciparum malaria transmission in areas threatened by artemisinin resistance and areas aiming for malaria elimination. Community treatment campaigns with artemisinin-based combination therapy in combination with the gametocytocidal primaquine dose target all age groups but no studies thus far have assessed the pharmacokinetics of this gametocytocidal drug in African children. We recruited forty children participating in a primaquine efficacy trial in Burkina Faso to study primaquine pharmacokinetics...
March 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28288632/unexpected-selections-of-plasmodium-falciparum-polymorphisms-in-previously-treatment-na%C3%A3-ve-areas-after-monthly-presumptive-administration-of-three-different-anti-malarial-drugs-in-liberia-1976-78
#16
Irina T Jovel, Anders Björkman, Cally Roper, Andreas Mårtensson, Johan Ursing
BACKGROUND: To assess the effect on malaria prevalence, village specific monthly administrations of pyrimethamine, chlorproguanil, chloroquine or placebo were given to children in four previously treatment-naïve Liberian villages, 1976-78. Plasmodium falciparum in vivo resistance developed to pyrimethamine only. Selection of molecular markers of P. falciparum resistance after 2 years of treatment are reported. METHODS: Blood samples were collected from 191 study children in a survey in 1978...
March 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28288098/mefloquine-targets-the-plasmodium-falciparum-80s-ribosome-to-inhibit-protein-synthesis
#17
Wilson Wong, Xiao-Chen Bai, Brad E Sleebs, Tony Triglia, Alan Brown, Jennifer K Thompson, Katherine E Jackson, Eric Hanssen, Danushka S Marapana, Israel S Fernandez, Stuart A Ralph, Alan F Cowman, Sjors H W Scheres, Jake Baum
Malaria control is heavily dependent on chemotherapeutic agents for disease prevention and drug treatment. Defining the mechanism of action for licensed drugs, for which no target is characterized, is critical to the development of their second-generation derivatives to improve drug potency towards inhibition of their molecular targets. Mefloquine is a widely used antimalarial without a known mode of action. Here, we demonstrate that mefloquine is a protein synthesis inhibitor. We solved a 3.2 Å cryo-electron microscopy structure of the Plasmodium falciparum 80S ribosome with the (+)-mefloquine enantiomer bound to the ribosome GTPase-associated centre...
March 13, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28285258/4-nitro-styrylquinoline-is-an-antimalarial-inhibiting-multiple-stages-of-plasmodium-falciparum-asexual-life-cycle
#18
Bracken F Roberts, Yongsheng Zheng, Jacob Cleaveleand, Sukjun Lee, Eunyoung Lee, Lawrence Ayong, Yu Yuan, Debopam Chakrabarti
Drugs against malaria are losing their effectiveness because of emerging drug resistance. This underscores the need for novel therapeutic options for malaria with mechanism of actions distinct from current antimalarials. To identify novel pharmacophores against malaria we have screened compounds containing structural features of natural products that are pharmacologically relevant. This screening has identified a 4-nitro styrylquinoline (SQ) compound with submicromolar antiplasmodial activity and excellent selectivity...
April 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28283009/-production-and-molecular-characterization-of-plasmodium-falciparum-recombinant-circumsporozoite-protein-with-37-nanp-and-4-nvdp-epitopes
#19
Yunus Uyar, Abdüssamed Akşit, Serkan Karaca, Şirin Sahra Ceylan, Merve Yürük
Malaria is caused by the protozoan parasite Plasmodium, the leading cause of death amongst the parasitic diseases. The disease is transmitted to human by the bites of female Anopheles mosquitoes. According to the World Health Organization (WHO) data, there were an estimated 214 million malaria cases and estimated 438.000 deaths occurred worldwide, in 2015. It is observed that 90% of all the deaths due to malaria occur in Africa. 78% of these cases were children who are under five years old. Intensive malaria interventions helped to reduce malaria incidence by 37% between 2000 and 2015...
January 2017: Mikrobiyoloji Bülteni
https://www.readbyqxmd.com/read/28279619/led-fluorescence-microscopy-novel-method-for-malaria-diagnosis-compared-with-routine-methods
#20
Riddhi Hathiwala, Preeti R Mehta, Gita Nataraj, Siddhi Hathiwala
Rapid and accurate diagnosis of malaria is the need of hour for effective management and controlling drug resistance. The conventional and gold-standard method, Light microscopy (LM), is time-consuming, requires trained staff and well-maintained equipments. The newly developed, rapid diagnostic tests (RDT) are fast and reliable, but give only qualitative results, are expensive and have short shelf life. Light Emission Diode fluorescence microscopy (LED FM) may provide a reliable alternative which can be used for routine diagnosis...
March 6, 2017: Journal of Infection and Public Health
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