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Malaria drug resistance

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https://www.readbyqxmd.com/read/27919897/genetic-evidence-for-cytochrome-b-qi-site-inhibition-by-4-1h-quinolone-3-diarylethers-and-antimycin-in-toxoplasma-gondii
#1
P Holland Alday, Igor Bruzual, Aaron Nilsen, Sovitj Pou, Rolf Winter, Choukri Ben Mamoun, Michael K Riscoe, J Stone Doggett
Toxoplasma gondii is an apicomplexan parasite that causes fatal and debilitating brain and eye disease. Endochin-like-quinolones (ELQs) are preclinical compounds that are efficacious against apicomplexan-caused diseases including toxoplasmosis, malaria and babesiosis. Of the ELQs, ELQ-316 has demonstrated the greatest efficacy against acute and chronic experimental toxoplasmosis. Although genetic analyses in other organisms have highlighted the importance of the cytochrome bc1 complex Qi site for ELQ sensitivity, the mechanism of action of ELQs against T...
December 5, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27919892/significant-divergence-in-sensitivity-to-antimalarial-drugs-between-neighboring-plasmodium-falciparum-populations-along-the-eastern-border-of-myanmar
#2
Weilin Zeng, Yao Bai, Meilian Wang, Zenglei Wang, Shuang Deng, Yonghua Ruan, Shi Feng, Zhaoqing Yang, Liwang Cui
Malaria parasites in different endemic areas display different levels of resistance to antimalarial drugs as the result of varied drug use histories. To provide updated knowledge of drug sensitivities during the malaria elimination phase in Southeast Asia, an epicenter of multidrug resistance, we determined in vitro susceptibilities of culture-adapted Plasmodium falciparum isolates from two eastern border regions (Wa and Kachin) of Myanmar to ten drugs. Despite their close proximity, the Kachin parasites displayed higher IC50 values than the Wa parasites to chloroquine, piperaquine, naphthoquine, mefloquine, quinine, pyrimethamine, pyronaridine, lumefantrine and dihydroartemisinin...
December 5, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27919257/global-priorities-for-research-and-the-relative-importance-of-different-research-outcomes-an-international-delphi-survey-of-malaria-research-experts
#3
Jo-Ann Mulligan, Lesong Conteh
BACKGROUND: As global research investment increases, attention inevitably turns to assessing and measuring the outcomes and impact from research programmes. Research can have many different outcomes such as producing advances in scientific knowledge, building research capacity and, ultimately, health and broader societal benefits. The aim of this study was to test the use of a Delphi methodology as a way of gathering views from malaria research experts on research priorities and eliciting relative valuations of the different types of health research impact...
December 6, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27919256/the-return-of-chloroquine-susceptible-plasmodium-falciparum-malaria-in-zambia
#4
Sydney Mwanza, Sudhaunshu Joshi, Michael Nambozi, Justin Chileshe, Phidelis Malunga, Jean-Bertin Bukasa Kabuya, Sebastian Hachizovu, Christine Manyando, Modest Mulenga, Miriam Laufer
BACKGROUND: Plasmodium falciparum resistance to anti-malarial drugs remains a major obstacle to malaria control and elimination. The parasite has developed resistance to every anti-malarial drug introduced for wide-scale treatment. However, the spread of resistance may be reversible. Malawi was the first country to discontinue chloroquine use due to widespread resistance. Within a decade of the removal of drug pressure, the molecular marker of chloroquine-resistant malaria had disappeared and the drug was shown to have excellent clinical efficacy...
December 5, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27914754/antiparasitic-and-disease-modifying-activity-of-nyctanthes-arbor-tristis-linn-in-malaria-an-exploratory-clinical-study
#5
Chhaya S Godse, Prakash S Tathed, Sameer S Talwalkar, Rama A Vaidya, Ashok J Amonkar, Akhil B Vaidya, Ashok D B Vaidya
BACKGROUND: An unceasing threat of drug resistance continuously poses demand for new antimalarial drugs. A scientific assessment of traditionally used antimalarial plants through reverse pharmacology is crucial for a fast track drug discovery. An Ayurvedic plant Nyctanthesarbor-tristis Linn. - (Parijat) had shown antimalarial activity, with a parasite clearance in 76.6% of 120 patients, in an earlier clinical study. OBJECTIVE: To further explore antimalarial potential of the plant through additional objective markers...
November 30, 2016: Journal of Ayurveda and Integrative Medicine
https://www.readbyqxmd.com/read/27912758/emerging-polymorphisms-in-falciparum-kelch-13-gene-in-northeastern-region-of-india
#6
Neelima Mishra, Ram Suresh Bharti, Prashant Mallick, Om Prakash Singh, Bina Srivastava, Roma Rana, Sobhan Phookan, Hardev Prasad Gupta, Pascal Ringwald, Neena Valecha
BACKGROUND: Recent reports of emergence and spread of artemisinin resistance in the Southeast Asia region, including Myanmar, pose a greater threat to malaria control and elimination in India. Whole genome sequencing studies have associated mutations in the K13 propeller gene (k13), PF3D7_1343700 with artemisinin resistance both in vitro and in vivo. The aim of the present study was to find the k13 gene polymorphisms in Plasmodium falciparum parasites from the three sites in the Northeast region of India, bordering Bangladesh and Myanmar...
December 3, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27903279/in-vitro-and-in-vivo-anti-malarial-activity-of-novel-harmine-analog-heat-shock-protein-90-inhibitors-a-possible-partner-for-artemisinin
#7
Abebe Genetu Bayih, Asongna Folefoc, Abu Naser Mohon, Scott Eagon, Marc Anderson, Dylan R Pillai
BACKGROUND: The emergence of artemisinin-resistant Plasmodium falciparum strains poses a serious challenge to the control of malaria. This necessitates the development of new anti-malarial drugs. Previous studies have shown that the natural beta-carboline alkaloid harmine is a promising anti-malarial agent targeting the P. falciparum heat-shock protein 90 (PfHsp90). The aim of this study was to test the anti-malarial activity of harmine analogues. METHODS: Forty-two harmine analogues were synthesized and the binding of these analogues to P...
December 1, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27896890/diterpenes-as-lead-molecules-against-neglected-tropical-diseases
#8
REVIEW
Marcus Vinícius Oliveira Barros de Alencar, João Marcelo de Castro E Sousa, Hercília Maria Lins Rolim, Maria das Graças Freire de Medeiros, Gilberto Santos Cerqueira, Fernanda Regina de Castro Almeida, Antônia Maria das Graças Lopes Citó, Paulo Michel Pinheiro Ferreira, José Arimatéia Dantas Lopes, Ana Amélia de Carvalho Melo-Cavalcante, Md Torequl Islam
Nowadays, neglected tropical diseases (NTDs) are reported to be present everywhere. Poor and developing areas in the world have received great attention to NTDs. Drug resistance, safety profile, and various challenges stimulate the search for alternative medications. Plant-based drugs are viewed with great interest, as they are believed to be devoid of side effects. Diterpenes, a family of essential oils, have showed attractive biological effects. A systematic review of the literature was carried out to summarize available evidences of diterpenes against NTDs...
November 29, 2016: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/27895269/stability-of-dihydroartemisinin-piperaquine-tablet-halves-during-prolonged-storage-under-tropical-conditions
#9
Eva Maria Hodel, Harparkash Kaur, Dianne J Terlouw
Dihydroartemisinin-piperaquine (DP) is recommended for the treatment of uncomplicated malaria, used in efforts to contain artemisinin resistance, and increasingly considered for mass drug administration. Because of the narrow therapeutic dose range and available tablet strengths, the manufacturers and World Health Organization recommended regimens involve breaking tablets into halves to accurately dose children according to body weight. Use of tablet fractions in programmatic settings under tropical conditions requires a highly stable product; however, the stability of DP tablet fractions is unknown...
November 28, 2016: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27886547/comprehensive-review-on-various-strategies-for-antimalarial-drug-discovery
#10
Mitali Mishra, Vikash K Mishra, Varsha Kashaw, Arun K Iyer, Sushil Kumar Kashaw
The resistance of malaria parasites to existing drugs carries on growing and progressively limiting our ability to manage this severe disease and finally lead to a massive global health burden. Till now, malaria control has relied upon the traditional quinoline, antifolate and artemisinin compounds. Very few new antimalarials were developed in the past 50 years. Among recent approaches, identification of novel chemotherapeutic targets, exploration of natural products with medicinal significance, covalent bitherapy having a dual mode of action into a single hybrid molecule and malaria vaccine development are explored heavily...
November 12, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27880887/de-novo-lead-optimization-of-triazine-derivatives-identifies-potent-antimalarials
#11
Ashutosh Shandilya, Nasimul Hoda, Sameena Khan, Ehtesham Jameel, Jitendra Kumar, B Jayaram
Malaria is a life-threatening disease caused by Plasmodium parasites among which Plasmodium falciparum is the most deadly. Due to the widespread resistance of the current antimalarial drugs, intense research efforts are focused on identification of new and potent antimalarials. We report here, a structure based drug discovery strategy for design of a series of effective and novel triazine based antimalarials. The X-ray structure of P. falciparum methyl transferase (PfPMT) is used as a target as it is unique to the parasite...
November 13, 2016: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/27879115/preface
#12
Avner Friedman, Mirosław Lachowicz, Urszula Ledzewicz, Monika Joanna Piotrowska, Zuzanna Szymanska
This volume was inspired by the topics presented at the international conference "Micro and Macro Systems in Life Sciences" which was held on Jun 8-12, 2015 in Będlewo, Poland. System biology is an approach which tries to understand how micro systems, at the molecular and cellular levels, affect macro systems such as organs, tissue and populations. Thus it is not surprising that a major theme of this volume evolves around cancer and its treatment. Articles on this topic include models for tumor induced angiogenesis, without and with delays, metastatic niche of the bone marrow, drug resistance and metronomic chemotherapy, and virotherapy of glioma...
February 1, 2017: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/27875528/effectiveness-of-seasonal-malaria-chemoprevention-in-children-under-ten-years-of-age-in-senegal-a-stepped-wedge-cluster-randomised-trial
#13
Badara Cissé, El Hadj Ba, Cheikh Sokhna, Jean Louis NDiaye, Jules F Gomis, Yankhoba Dial, Catherine Pitt, Mouhamed NDiaye, Matthew Cairns, Ernest Faye, Magatte NDiaye, Aminata Lo, Roger Tine, Sylvain Faye, Babacar Faye, Ousmane Sy, Lansana Konate, Ekoue Kouevijdin, Clare Flach, Ousmane Faye, Jean-Francois Trape, Colin Sutherland, Fatou Ba Fall, Pape M Thior, Oumar K Faye, Brian Greenwood, Oumar Gaye, Paul Milligan
BACKGROUND: Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ), given each month during the transmission season, is recommended for children living in areas of the Sahel where malaria transmission is highly seasonal. The recommendation for SMC is currently limited to children under five years of age, but, in many areas of seasonal transmission, the burden in older children may justify extending this age limit. This study was done to determine the effectiveness of SMC in Senegalese children up to ten years of age...
November 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27874068/identification-of-inhibitors-that-dually-target-the-new-permeability-pathway-and-dihydroorotate-dehydrogenase-in-the-blood-stage-of-plasmodium-falciparum
#14
Benjamin K Dickerman, Brendan Elsworth, Simon A Cobbold, Catherine Q Nie, Malcolm J McConville, Brendan S Crabb, Paul R Gilson
Plasmodium parasites are responsible for the devastating disease malaria that affects hundreds of millions of people each year. Blood stage parasites establish new permeability pathways (NPPs) in infected red blood cell membranes to facilitate the uptake of nutrients and removal of parasite waste products. Pharmacological inhibition of the NPPs is expected to lead to nutrient starvation and accumulation of toxic metabolites resulting in parasite death. Here, we have screened a curated library of antimalarial compounds, the MMV Malaria Box, identifying two compounds that inhibit NPP function...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872816/evidence-of-triple-mutant-pfdhps-isgnga-haplotype-in-plasmodium-falciparum-isolates-from-north-east-india-an-analysis-of-sulfadoxine-resistant-haplotype-selection
#15
Manuj K Das, Sumi Chetry, Mohan C Kalita, Prafulla Dutta
BACKGROUND: North-east region of India has consistent role in the spread of multi drug resistant Plasmodium (P.) falciparum to other parts of Southeast Asia. After rapid clinical treatment failure of Artemisinin based combination therapy-Sulphadoxine/Pyrimethamine (ACT-SP) chemoprophylaxis, Artemether-Lumefantrine (ACT-AL) combination therapy was introduced in the year 2012 in this region for the treatment of uncomplicated P. falciparum malaria. In a DNA sequencing based polymorphism analysis, seven codons of P...
December 2016: Genomics Data
https://www.readbyqxmd.com/read/27872647/antimalarial-properties-of-aqueous-crude-extracts-of-gynostemma-pentaphyllum-and-moringa-oleifera-leaves-in-combination-with-artesunate-in-plasmodium-berghei-infected-mice
#16
Voravuth Somsak, Preeyanuch Borkaew, Chokdee Klubsri, Kittiyaporn Dondee, Panatda Bootprom, Butsarat Saiphet
Due to the emergence and spread of malaria parasite with resistance to antimalarial drugs, discovery and development of new, safe, and affordable antimalarial are urgently needed. In this respect, medicinal plant extracts are targets to optimize antimalarial actions and restore efficacy of standard antimalarial drugs. The present study was aimed at determining the antimalarial activities of Gynostemma pentaphyllum and Moringa oleifera leaf extracts in combination with artesunate against Plasmodium berghei-infected mice...
2016: Journal of Tropical Medicine
https://www.readbyqxmd.com/read/27866919/in-vitro-sensitivity-of-antimalarial-drugs-and-correlation-with-clinico-parasitological-response-following-treatment-with-a-3-day-artesunate-mefloquine-combination-in-patients-with-falciparum-malaria-along-the-thai-myanmar-border
#17
Phunuch Muhamad, Artitaya Thiengsusuk, Papichaya Phompradit, Kesara Na-Bangchang
A 3-day artesunate-mefloquine combination therapy has been using as first-line treatment for acute uncomplicated Plasmodium falciparum malaria in Thailand since 1995 on the background of mefloquine resistance. The aim of the present study was to assess sensitivity of P. falciparum isolates (n=44) in an area along the Thai-Myanmar border (year 2009) to artesunate, mefloquine, chloroquine and quinine, including their correlation with clinico-parasitological response. Twenty, 19, and 5 isolates were collected from patients with 'Adequate Clinical and Parasitological Response (ACPR)', 'Late Parasitological Failure (LPF)' and 're-infection', respectively...
November 17, 2016: Acta Tropica
https://www.readbyqxmd.com/read/27864679/prescription-of-antimalarial-drugs-in-the-pediatric-ward-of-the-national-hospital-of-lamord%C3%A3-in-niamey
#18
A Soumana, M Kamaye, B Issofou, H Dima, B Daouda, O N'Diaye, G Sall
In Niger, malaria is a major public health problem, due to the high number of deaths that are attributable to it and because of its heavy weight and socioeconomic status. The objective of this study was to contribute to the inventory of medical practices to rationalize the use of medicines and minimize the resistance phenomenon. This is a prospective study, which took place from May 1 to July 31, 2009, in the pediatric ward of the National Hospital of Lamordé. It concerned children aged from 0 to 14 years hospitalized and having received one or more antimalarial drugs during at least 24 h...
November 18, 2016: Bulletin de la Société de Pathologie Exotique
https://www.readbyqxmd.com/read/27861509/parasitological-clearance-rates-and-drug-concentrations-of-a-fixed-dose-combination-of-azithromycin-chloroquine-in-asymptomatic-pregnant-women-with-plasmodium-falciparum-parasitemia-an-open-label-non-comparative-study-in-sub-saharan-africa
#19
Kamija Phiri, Joshua Kimani, George A Mtove, Qinying Zhao, Ricardo Rojo, Jeffery Robbins, Stephan Duparc, Ayman Ayoub, Pol Vandenbroucke
BACKGROUND: Malaria remains one of the most important causes of morbidity and mortality in pregnant women and their newborn babies in sub-Saharan Africa. Intermittent preventive treatment in pregnancy (IPTp) is recommended by the World Health Organization (WHO) to reduce the burden of disease and improve maternal and neonatal survival and general health. Due to the growing resistance to sulfadoxine-pyrimethamine (SP), the current WHO-recommended drug for IPTp, identification of new and effective drugs is an urgent priority...
2016: PloS One
https://www.readbyqxmd.com/read/27860197/crispr-cas9-the-ultimate-weapon-to-battle-infectious-diseases
#20
REVIEW
M Doerflinger, W Forsyth, G Ebert, M Pellegrini, M J Herold
Infectious diseases are a leading cause of death worldwide. Novel therapeutics are urgently required to treat multidrug-resistant organisms such as Mycobacterium tuberculosis and to mitigate morbidity and mortality caused by acute infections such as malaria and dengue fever virus as well as chronic infections such as human immunodeficiency virus-1 and hepatitis B virus. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, which has revolutionized biomedical research, holds great promise for the identification and validation of novel drug targets...
November 16, 2016: Cellular Microbiology
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