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https://www.readbyqxmd.com/read/29140232/country-wide-surveillance-of-molecular-markers-of-antimalarial-drug-resistance-in-senegal-by-use-of-positive-malaria-rapid-diagnostic-tests
#1
Magatte Ndiaye, Doudou Sow, Sidsel Nag, Khadime Sylla, Roger Clement Tine, Jean Louis Ndiaye, Aminata Collé Lo, Oumar Gaye, Babacar Faye, Michael Alifrangis
In Senegal, antimalarial drugs used in treatment and prevention of malaria are one of the main reasons for the current success in controlling malaria. However, the successful control of malaria is highly dependent on continued effectiveness of these drugs which may be compromised by the spread of drug resistance. Therefore, surveillance of drug resistance in the malaria parasites is essential. The objective of this pilot study was to test the feasibility of routinely sampled malaria rapid diagnostic tests (RDTs) at a national scale to assess the temporal changes in the molecular profiles of antimalarial drug resistance markers of Plasmodium falciparum parasites...
November 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29138944/design-synthesis-conformational-and-molecular-docking-study-of-some-novel-acyl-hydrazone-based-molecular-hybrids-as-antimalarial-and-antimicrobial-agents
#2
Parvin Kumar, Kulbir Kadyan, Meenakshi Duhan, Jayant Sindhu, Vineeta Singh, Baljeet Singh Saharan
BACKGROUND: Acyl hydrazones are an important class of heterocyclic compounds promising pharmacological characteristics. Malaria is a life-threatening mosquito-borne blood disease caused by a plasmodium parasite. In some places, malaria can be treated and controlled with early diagnosis. However, some countries lack the resources to do this effectively. RESULTS: The present work involves the design and synthesis of some novel acyl hydrazone based molecular hybrids of 1,4-dihydropyridine and pyrazole (5a-g)...
November 14, 2017: Chemistry Central Journal
https://www.readbyqxmd.com/read/29138320/structural-basis-for-antibody-recognition-of-the-nanp-repeats-in-plasmodium-falciparum-circumsporozoite-protein
#3
David Oyen, Jonathan L Torres, Ulrike Wille-Reece, Christian F Ockenhouse, Daniel Emerling, Jacob Glanville, Wayne Volkmuth, Yevel Flores-Garcia, Fidel Zavala, Andrew B Ward, C Richter King, Ian A Wilson
Acquired resistance against antimalarial drugs has further increased the need for an effective malaria vaccine. The current leading candidate, RTS,S, is a recombinant circumsporozoite protein (CSP)-based vaccine against Plasmodium falciparum that contains 19 NANP repeats followed by a thrombospondin repeat domain. Although RTS,S has undergone extensive clinical testing and has progressed through phase III clinical trials, continued efforts are underway to enhance its efficacy and duration of protection. Here, we determined that two monoclonal antibodies (mAbs 311 and 317), isolated from a recent controlled human malaria infection trial exploring a delayed fractional dose, inhibit parasite development in vivo by at least 97%...
November 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29129935/antimalarial-use-of-malagasy-plants-is-poorly-correlated-with-performance-in-antimalarial-bioassays
#4
Wendy L Applequist, Michel Ratsimbason, Alyse Kuhlman, Stephan Rakotonandrasana, Vincent Rasamison, David G I Kingston
Bioassay screening of plant extracts can identify unique lead compounds for drug development, but the "hit rate" from random screening is very low. Targeted screening of medicinal plants has been repeatedly reported to increase the percentage of samples displaying bioactivity. Contrarily, Maranz (2012) suggested that African antimalarial plants were unsuitable sources of antimalarial drugs because high prevalence of malaria would result in rapid evolution of resistance to active compounds that directly targeted the parasite...
March 2017: Economic Botany
https://www.readbyqxmd.com/read/29128848/antimalarial-activity-of-malaria-box-compounds-against-plasmodium-falciparum-clinical-isolates
#5
Jersley D Chirawurah, Felix Ansah, Prince B Nyarko, Samuel Duodu, Yaw Aniweh, Gordon A Awandare
Malaria remains a major cause of childhood deaths in resource-limited settings. In the absence of an effective vaccine, drugs and other interventions have played very significant roles in combating the scourge of malaria. The recent reports of resistance to artemisinin necessitate the need for new antimalarial drugs with novel mechanisms of action. Towards the development of new, affordable and easily accessible antimalarial drugs for endemic regions, the Medicines for Malaria Venture (MMV) assembled a total of 400 active antimalarial compounds called the Malaria Box...
October 16, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29128746/human-serum-albumin-binding-of-certain-antimalarials
#6
Olivera S Marković, Ilija N Cvijetić, Mario V Zlatović, Igor M Opsenica, Jelena M Konstantinović, Nataša V Terzić Jovanović, Bogdan A Šolaja, Tatjana Ž Verbić
Interactions between eight in-house synthesized aminoquinolines, along with well-known chloroquine, and human serum albumin (HSA) have been studied by fluorescence spectroscopy. The synthesized aminoquinolines, despite being structurally diverse, were found to be very potent antimalarials. Fluorescence measurements indicate that three compounds having additional thiophene or benzothiophene substructure bind more strongly to HSA than other studied compounds. Competitive binding experiments indicate that these three compounds bind significantly stronger to warfarin compared to diazepam binding site...
November 9, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/29128302/corrigendum-to-genetic-diversity-of-next-generation-antimalarial-targets-a-baseline-for-drug-resistance-surveillance-programmes-int-j-parasitol-drugs-and-drug-resist-7-2017-174-180
#7
Ana Rita Gomes, Matt Ravenhall, Ernest Diez Benavente, Arthur Talman, Colin Sutherland, Cally Roper, Taane G Clark, Susana Campino
No abstract text is available yet for this article.
November 6, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29127189/autophagy-promotes-escape-from-phosphatidylinositol-3-kinase-inhibition-in-estrogen-receptor-positive-breast-cancer
#8
Wei Yang, Sarah R Hosford, Nicole A Traphagen, Kevin Shee, Eugene Demidenko, Stephanie Liu, Todd W Miller
Hyperactivation of the PI3K pathway has been implicated in resistance to antiestrogen therapies in estrogen receptor α (ER)-positive breast cancer, prompting the development of therapeutic strategies to inhibit this pathway. Autophagy has tumor-promoting and -suppressing roles and has been broadly implicated in resistance to anticancer therapies, including antiestrogens. Chloroquine (CQ) is an antimalarial and amebicidal drug that inhibits autophagy in mammalian cells and human tumors. Herein, we observed that CQ inhibited proliferation and autophagy in ER(+) breast cancer cells...
November 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29126722/synthesis-%C3%AE-hematin-inhibition-studies-and-antimalarial-evaluation-of-new-dehydroxy-isoquine-derivatives-against-plasmodium-berghei-a-promising-antimalarial-agent
#9
Edgar A Valverde, Angel H Romero, María E Acosta, Neira Gamboa, Genesis Henriques, Juan R Rodrigues, Carlos Ciangherotti, Simón E López
Many people are affected by Malaria around the world, and the parasite is developing resistance against available drugs. Currently, isoquine and N-tert-butyl isoquine are some of the most promising antimalarial candidates that have already reached Phase I and II clinical trials, respectively. Nevertheless, pharmacodynamic studies have demonstrated that isoquine is highly sensitive to form O-glucuronide metabolite, which may affect its accumulation in tissues. To avoid the O-glucuronide formation and its negative influence in the accumulation process, a series of novel five dehydroxy isoquine derivatives were designed and prepared herein as potential antimalarial agents...
October 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29125042/molecular-surveillance-of-chloroquine-drug-resistance-markers-pfcrt-and-pfmdr1-among-imported-plasmodium-falciparum-malaria-in-qatar
#10
Anushree Acharya, Devendra Bansal, Praveen K Bharti, Fahmi Y Khan, Salem Abusalah, Ashraf Elmalik, Mohammed ElKhalifa, Pradyumna K Mohapatra, Jagadish Mahanta, Rakesh Sehgal, Neeru Singh, Ali A Sultan
Imported malaria has been a great challenge for public health in Qatar due to influx of large number of migrant workers. Antimalarial drug resistance has emerged as one of the greatest challenges facing malaria control today. Monitoring parasite haplotypes that predict susceptibility to major antimalarial can guide treatment policies. This study aimed to determine molecular drug resistance pattern in imported malaria cases in Qatar. Blood samples from the uncomplicated P. falciparum malaria patients were collected at Hamad General Hospital, HMC, Doha, Qatar...
November 10, 2017: Pathogens and Global Health
https://www.readbyqxmd.com/read/29123551/discovery-of-antimalarial-drugs-from-streptomycetes-metabolites-using-a-metabolomic-approach
#11
REVIEW
Siti Junaidah Ahmad, Mohd Badrin Hanizam Abdul Rahim, Syarul Nataqain Baharum, Mohd Shukri Baba, Noraziah Mohamad Zin
Natural products continue to play an important role as a source of biologically active substances for the development of new drug. Streptomyces, Gram-positive bacteria which are widely distributed in nature, are one of the most popular sources of natural antibiotics. Recently, by using a bioassay-guided fractionation, an antimalarial compound, Gancidin-W, has been discovered from these bacteria. However, this classical method in identifying potentially novel bioactive compounds from the natural products requires considerable effort and is a time-consuming process...
2017: Journal of Tropical Medicine
https://www.readbyqxmd.com/read/29123481/development-in-assay-methods-for-in-vitro-antimalarial-drug-efficacy-testing-a-systematic-review
#12
REVIEW
Shweta Sinha, Phulen Sarma, Rakesh Sehgal, Bikash Medhi
The emergence and spread of drug resistance are the major challenges in malaria eradication mission. Besides various strategies laid down by World Health Organization, such as vector management, source reduction, early case detection, prompt treatment, and development of new diagnostics and vaccines, nevertheless the need for new and efficacious drugs against malaria has become a critical priority on the global malaria research agenda. At several screening stages, millions of compounds are screened (1,000-2,000,000 compounds per screening campaign), before pre-clinical trials to select optimum lead...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29119735/poly-d-l-lactic-co-glycolic-acid-based-artesunate-nanoparticles-formulation-antimalarial-and-toxicity-assessments
#13
Kabiru Dauda, Zulaikha Busari, Olajumoke Morenikeji, Funmilayo Afolayan, Oyetunde Oyeyemi, Jairam Meena, Debasis Sahu, Amulya Panda
OBJECTIVE: The aim of this study was to formulate polymer-based artesunate nanoparticles for malaria treatment. METHODS: Artesunate was loaded with poly(D,L-lactic-co-glycolic acid) (PLGA) by solvent evaporation from an oil-in-water single emulsion. Nanoparticles were characterized by X-ray diffraction and differential scanning calorimetry analyses. In vivo antimalarial studies at 4 mg/kg were performed on Swiss male albino mice infected with Plasmodium berghei...
2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/29110722/molecular-markers-for-artemisinin-and-partner-drug-resistance-in-natural-plasmodium-falciparum-populations-following-increased-insecticide-treated-net-coverage-along-the-slope-of-mount-cameroon-cross-sectional-study
#14
Tobias O Apinjoh, Regina N Mugri, Olivo Miotto, Hanesh F Chi, Rolland B Tata, Judith K Anchang-Kimbi, Eleanor M Fon, Delphine A Tangoh, Robert V Nyingchu, Christopher Jacob, Roberto Amato, Abdoulaye Djimde, Dominic Kwiatkowski, Eric A Achidi, Alfred Amambua-Ngwa
BACKGROUND: Drug resistance is one of the greatest challenges of malaria control programmes, with the monitoring of parasite resistance to artemisinins or to Artemisinin Combination Therapy (ACT) partner drugs critical to elimination efforts. Markers of resistance to a wide panel of antimalarials were assessed in natural parasite populations from southwestern Cameroon. METHODS: Individuals with asymptomatic parasitaemia or uncomplicated malaria were enrolled through cross-sectional surveys from May 2013 to March 2014 along the slope of mount Cameroon...
November 6, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/29109477/plasmodium-uis3-sequesters-host-lc3-to-avoid-elimination-by-autophagy-in-hepatocytes
#15
Eliana Real, Lénia Rodrigues, Ghislain G Cabal, Francisco J Enguita, Liliana Mancio-Silva, João Mello-Vieira, Wandy Beatty, Iset M Vera, Vanessa Zuzarte-Luís, Tiago N Figueira, Gunnar R Mair, Maria M Mota
The causative agent of malaria, Plasmodium, replicates inside a membrane-bound parasitophorous vacuole (PV), which shields this intracellular parasite from the cytosol of the host cell (1) . One common threat for intracellular pathogens is the homeostatic process of autophagy, through which cells capture unwanted intracellular material for lysosomal degradation (2) . During the liver stage of a malaria infection, Plasmodium parasites are targeted by the autophagy machinery of the host cell, and the PV membrane (PVM) becomes decorated with several autophagy markers, including LC3 (microtubule-associated protein 1 light chain 3) (3,4) ...
November 6, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/29097636/antiplasmodial-efficacy-of-calotropis-gigantea-l-against-plasmodium-falciparum-3d7-strain-and-plasmodium-berghei-anka
#16
P V V Satish, D Santha Kumari, K Sunita
BACKGROUND & OBJECTIVES: Malaria is a deadly parasitic disease, having a high rate of incidence and mortality across the world. The spread and development of resistance against chemical insecticides is one of the major problems associated with malaria treatment and control. Hence, plant based formulations may serve as an alternative source towards development of new drugs for treatment of malaria. The present study was aimed to evaluate the in vitro antiplasmodial activities of leaf, stem and flower of Calotropis gigantea against chloroquine-sensitive Plasmodium falciparum (3D7 strain) and its cytotoxicity against THP-1 cell lines...
July 2017: Journal of Vector Borne Diseases
https://www.readbyqxmd.com/read/29090371/cutaneous-manifestations-of-dermatomyositis-a-comprehensive-review
#17
REVIEW
Carlo Mainetti, Benedetta Terziroli Beretta-Piccoli, Carlo Selmi
Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by the presence of skin lesions and inflammation of skeletal muscles; however, this feature may be absent in amyopathic DM. DM is a rare disease, occurring at any age, and has two peaks of incidence: one in childhood between 5 and 15 years of age and one in adulthood between 40 and 60 years, with a female preponderance. DM has been associated with malignancy; therefore, every newly diagnosed patient should undergo screening investigations, but evidence-based guidelines on their extension are lacking...
October 31, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29083100/mefloquine-for-preventing-malaria-during-travel-to-endemic-areas
#18
REVIEW
Maya Tickell-Painter, Nicola Maayan, Rachel Saunders, Cheryl Pace, David Sinclair
BACKGROUND: Mefloquine is one of four antimalarial agents commonly recommended for preventing malaria in travellers to malaria-endemic areas. Despite its high efficacy, there is controversy about its psychological side effects. OBJECTIVES: To summarize the efficacy and safety of mefloquine used as prophylaxis for malaria in travellers. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published on the Cochrane Library; MEDLINE; Embase (OVID); TOXLINE (https://toxnet...
October 30, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29082025/prevalence-of-substandard-and-falsified-artemisinin-based-combination-antimalarial-medicines-on-bioko-island-equatorial-guinea
#19
Harparkash Kaur, Elizabeth Louise Allan, Ibrahim Mamadu, Zoe Hall, Michael D Green, Isabel Swamidos, Prabha Dwivedi, Maria Julia Culzoni, Facundo M Fernandez, Guillermo Garcia, Dianna Hergott, Feliciano Monti
INTRODUCTION: Poor-quality artemisinin-containing antimalarials (ACAs), including falsified and substandard formulations, pose serious health concerns in malaria endemic countries. They can harm patients, contribute to the rise in drug resistance and increase the public's mistrust of health systems. Systematic assessment of drug quality is needed to gain knowledge on the prevalence of the problem, to provide Ministries of Health with evidence on which local regulators can take action...
2017: BMJ Global Health
https://www.readbyqxmd.com/read/29082016/randomised-controlled-trial-of-two-sequential-artemisinin-based-combination-therapy-regimens-to-treat-uncomplicated-falciparum-malaria-in-african-children-a-protocol-to-investigate-safety-efficacy-and-adherence
#20
Henk Dfh Schallig, Halidou Tinto, Patrick Sawa, Harparkash Kaur, Stephan Duparc, Deus S Ishengoma, Pascal Magnussen, Michael Alifrangis, Colin J Sutherland
BACKGROUND: Management of uncomplicated Plasmodium falciparum malaria relies on artemisinin-based combination therapies (ACTs). These highly effective regimens have contributed to reductions in malaria morbidity and mortality. However, artemisinin resistance in Asia and changing parasite susceptibility to ACT in Africa have now been well documented. Strategies that retain current ACT as efficacious treatments are urgently needed. METHODS: We present an open-label, randomised three-arm clinical trial protocol in three African settings representative of varying malaria epidemiology to investigate whether prolonged ACT-based regimens using currently available formulations can eliminate potentially resistant parasites...
2017: BMJ Global Health
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