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https://www.readbyqxmd.com/read/29793059/longitudinal-surveillance-of-drug-resistance-in-plasmodium-falciparum-isolates-from-the-china-myanmar-border-reveals-persistent-circulation-of-multidrug-resistant-parasites
#1
Yao Bai, Jiaqi Zhang, Jinting Geng, Shiling Xu, Shuang Deng, Weilin Zeng, Zenglei Wang, Huguette Gaelle Ngassa Mbenda, Jie Zhang, Na Li, Yanrui Wu, Cuiying Li, Huae Liu, Yonghua Ruan, Yaming Cao, Zhaoqing Yang, Liwang Cui
Multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion of Southeast Asia is a major threat to malaria elimination and requires close surveillance. In this study, we collected 107 longitudinal clinical samples of P. falciparum in 2007-2012 from the malaria hypoendemic region of the China-Myanmar border and measured their in vitro susceptibilities to 10 antimalarial drugs. Overall, parasites had significantly different IC50 values to all the drugs tested as compared to the reference 3D7 strain...
May 21, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29791525/2-3-8-trisubstituted-quinolines-with-antimalarial-activity
#2
Pablo D G Martinez, Susann H Krake, Maitia L Poggi, Simon F Campbell, Paul A Willis, Luiz C Dias
Combination therapy drugs are considered a fundamental way to control malaria as it mimimizes the risk of emergence of resistance to the individual partner drugs. Consequently, this type of therapy constitutes a driving force for the discovery of new drugs with different modes of action, since this will provide options for combining different drugs to achieve the optimum antimalarial treatment. In this context, a 2,3,8-trisubstitued quinoline compound was found in a high throughput screen (HTS) to show an excellent inhibition of P...
May 21, 2018: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/29791438/identity-by-descent-analyses-for-measuring-population-dynamics-and-selection-in-recombining-pathogens
#3
Lyndal Henden, Stuart Lee, Ivo Mueller, Alyssa Barry, Melanie Bahlo
Identification of genomic regions that are identical by descent (IBD) has proven useful for human genetic studies where analyses have led to the discovery of familial relatedness and fine-mapping of disease critical regions. Unfortunately however, IBD analyses have been underutilized in analysis of other organisms, including human pathogens. This is in part due to the lack of statistical methodologies for non-diploid genomes in addition to the added complexity of multiclonal infections. As such, we have developed an IBD methodology, called isoRelate, for analysis of haploid recombining microorganisms in the presence of multiclonal infections...
May 23, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29789805/in-silico-knockout-screening-of-plasmodium-falciparum-reactions-and-prediction-of-novel-essential-reactions-by-analysing-the-metabolic-network
#4
Jelili Oyelade, Itunuoluwa Isewon, Efosa Uwoghiren, Olufemi Aromolaran, Olufunke Oladipupo
Malaria is an infectious disease that affects close to half a million individuals every year and Plasmodium falciparum is a major cause of malaria. The treatment of this disease could be done effectively if the essential enzymes of this parasite are specifically targeted. Nevertheless, the development of the parasite in resisting existing drugs now makes discovering new drugs a core responsibility. In this study, a novel computational model that makes the prediction of new and validated antimalarial drug target cheaper, easier, and faster has been developed...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29785925/comparison-of-two-genotyping-methods-for-distinguishing-recrudescence-from-reinfection-in-antimalarial-drug-efficacy-effectiveness-trials
#5
Joseph R M Fulakeza, Rachel L Banda, Trancizeo R Lipenga, Dianne J Terlouw, Standwell C Nkhoma, Eva Maria Hodel
Genotyping of allelic variants of Plasmodium falciparum merozoite surface proteins 1 and 2 ( msp-1 and msp-2 ), and the glutamate-rich protein is the gold standard for distinguishing reinfections from recrudescences in antimalarial drug trials. We compared performance of the recently developed 24-single-nucleotide polymorphism (SNP) Barcoding Assay against msp-1 and msp-2 genotyping in a cluster-randomized effectiveness trial of artemether-lumefantrine and dihydroartemisinin-piperaquine in Malawi. Rates of recrudescence and reinfection estimated by the two methods did not differ significantly (Fisher's exact test; P = 0...
May 21, 2018: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29784841/the-metabolism-of-piperaquine-to-its-antiplasmodial-metabolites-and-their-pharmacokinetic-profiles-in-healthy-volunteers
#6
Huixiang Liu, Hongchang Zhou, Tianyu Cai, Aijuan Yang, Meitong Zang, Jie Xing
As a partner antimalarial for artemisinin drug-based combination therapy (ACT), piperaquine (PQ) can be metabolized into two major metabolites, including piperaquine N -oxide (M1) and N , N -dioxide (M2). To better understand the antimalarial potency of PQ, the antimalarial activity of PQ metabolites (M1 and M2) was studied in vitro ( Plasmodium strains Pf 3D7 and Pf Dd2) and in vivo (murine Plasmodium yoelii ) in this study. The recrudescence and survival time of infected mice were also recorded after drug treatment...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29779499/efficacy-of-artemisinin-naphthoquine-phosphate-against-schistosoma-haematobium-adult-flukes-dose-effect-relationship-and-tegumental-alterations
#7
S N El-Beshbishi, S El Bardicy, M Tadros, M Ayoub, A Taman
Schistosoma haematobium and Schistosoma mansoni infections have broadly overlapping geographical distributions. Praziquantel is the only treatment for human schistosomiasis, so drug tolerance and/or resistance are major concerns. Artemisinin-naphthoquine phosphate (CO-ArNp), an artemisinin-based combination therapy endorsed by the World Health Organization as a gold standard therapy for malaria, has also been identified as a promising treatment for S. mansoni. In this in vitro study, we tested the effect of 1-40 μg/ml CO-ArNp on S...
May 21, 2018: Journal of Helminthology
https://www.readbyqxmd.com/read/29775778/the-genus-cordyceps-an-extensive-review-of-its-traditional-uses-phytochemistry-and-pharmacology
#8
REVIEW
Opeyemi Joshua Olatunji, Jian Tang, Adesola Tola, Florence Auberon, Omolara Oluwaniyi, Zhen Ouyang
The genus Cordyceps has about 750 identified species which are distributed in many regions of the World, but mainly found in South Asia, Europe and North America. The species of the genus are highly priced and are widely used as food and medicine for the treatment of various ailments. This present review compiles literature information on the ethno-medicinal, phytochemistry and pharmacological properties of species in the genus Cordyceps. In addition, the review also suggest recommendations for the future researches...
May 15, 2018: Fitoterapia
https://www.readbyqxmd.com/read/29773230/medications-received-by-patients-with-juvenile-dermatomyositis
#9
Takayuki Kishi, Nastaran Bayat, Michael M Ward, Adam M Huber, Lan Wu, Gulnara Mamyrova, Ira N Targoff, William J Warren-Hicks, Frederick W Miller, Lisa G Rider
OBJECTIVE: Few controlled studies are available to guide treatment decisions in juvenile dermatomyositis (JDM). This study evaluated therapies received, changes of treatment over time, and factors associated with medication choices in JDM. METHODS: We performed a retrospective analysis of the number and type of therapies and duration of treatment for 320 patients with JDM enrolled in a North American registry. Kaplan-Meier and logistic regression analysis were used to assess the association of demographic and clinical features and autoantibodies with medication usage...
March 28, 2018: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/29764451/phenotypic-and-genotypic-characterization-of-thai-isolates-of-plasmodium-falciparum-after-an-artemisinin-resistance-containment-project
#10
Thunyapit Thita, Pimrat Jadsri, Jarupatr Thamkhantho, Toon Ruang-Areerate, Nantana Suwandittakul, Naruemon Sitthichot, Kittiya Mahotorn, Peerapan Tan-Ariya, Mathirut Mungthin
BACKGROUND: In Thailand, artemisinin-based combination therapy (ACT) has been used to treat uncomplicated falciparum malaria since 1995. Unfortunately, artemisinin resistance has been reported from Thailand and other Southeast Asian countries since 2003. Malarone® , a combination of atovaquone-proguanil (ATQ-PG), has been used to cease artemisinin pressure in some areas along Thai-Cambodia border, as part of an artemisinin resistance containment project since 2009. This study aimed to determine genotypes and phenotypes of Plasmodium falciparum isolates collected from the Thai-Cambodia border after the artemisinin resistance containment project compared with those collected before...
May 15, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29764407/are-we-doing-enough-to-prevent-poor-quality-antimalarial-medicines-in-the-developing-world
#11
Erin J Walker, Gregory M Peterson, James Grech, Evie Paragalli, Jackson Thomas
BACKGROUND: Malaria is a deadly parasitic disease that affects more than 3 billion people worldwide, in predominantly resource-poor countries. Despite malaria being preventable and treatable, a large number of adults and children, mostly in Africa, die from this disease each year. One contributor to needless morbidity and mortality is the production and distribution of poor-quality antimalarial medicines; indeed, it is estimated that over 122,000 deaths of children under 5 years of age in sub-Saharan countries were caused by poor-quality antimalarial medicines, in 2013 alone...
May 15, 2018: BMC Public Health
https://www.readbyqxmd.com/read/29758416/drug-targets-for-resistant-malaria-historic-to-future-perspectives
#12
REVIEW
Sahil Kumar, T R Bhardwaj, D N Prasad, Rajesh K Singh
New antimalarial targets are the prime need for the discovery of potent drug candidates. In order to fulfill this objective, antimalarial drug researches are focusing on promising targets in order to develop new drug candidates. Basic metabolism and biochemical process in the malaria parasite, i.e. Plasmodium falciparum can play an indispensable role in the identification of these targets. But, the emergence of resistance to antimalarial drugs is an escalating comprehensive problem with the progress of antimalarial drug development...
May 11, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29758050/an-assessment-of-false-positive-rates-for-malaria-rapid-diagnostic-tests-caused-by-non-plasmodium-infectious-agents-and-immunological-factors
#13
Michelle L Gatton, Sadmir Ciketic, John W Barnwell, Qin Cheng, Peter L Chiodini, Sandra Incardona, David Bell, Jane Cunningham, Iveth J González
BACKGROUND: Malaria rapid diagnostic tests (RDTs) can produce false positive (FP) results in patients with human African trypanosomiasis and rheumatoid factor (RF), but specificity against other infectious agents and immunological factors is largely unknown. Low diagnostic specificity caused by cross-reactivity may lead to over-estimates of the number of malaria cases and over-use of antimalarial drugs, at the cost of not diagnosing and treating the true underlying condition. METHODS: Data from the WHO Malaria RDT Product Testing Programme was analysed to assess FP rates of 221 RDTs against four infectious agents (Chagas, dengue, Leishmaniasis and Schistosomiasis) and four immunological factors (anti-nuclear antibody, human anti-mouse antibody (HAMA), RF and rapid plasma regain)...
2018: PloS One
https://www.readbyqxmd.com/read/29757923/the-antimalarial-drug-artesunate-attenuates-cardiac-injury-in-a-rodent-model-of-myocardial-infarction
#14
Areeg I Khan, Amar Kapoor, Jianmin Chen, Lukas Martin, Mara Rogazzo, Thomas Mercier, Laurent Decosterd, Massimo Collino, Christoph Thiemermann
Ischemic heart disease remains the leading cause of morbidity and mortality in the Western world. Artesunate is the WHO-recommended drug of choice for complicated malaria (with organ failure). The administration of high doses of artesunate is safe in healthy volunteers (up to 8 mg/kg i.v.) and patients with severe malaria (2.4 mg/kg i.v.). We investigated the effects of artesunate (1 mg/kg) or its active metabolite dihydroartemisinin (DHA; 0.1 mg/kg) in a model of transient myocardial ischemia/reperfusion (I/R) and evaluated the mechanism of action of the observed cardioprotective effects of artesunate and DHA...
June 2018: Shock
https://www.readbyqxmd.com/read/29754074/structure-activity-relationship-of-new-antimalarial-1-aryl-3-susbtituted-propanol-derivatives-synthesis-preliminary-toxicity-profiling-parasite-life-cycle-stage-studies-target-exploration-and-targeted-delivery
#15
Miguel Quiliano, Adriana Pabón, Ernest Moles, Leonardo Bonilla-Ramirez, Isabelle Fabing, Kim Y Fong, Diego A Nieto-Aco, David W Wright, Juan C Pizarro, Ariane Vettorazzi, Adela López de Cerain, Eric Deharo, Xavier Fernández-Busquets, Giovanny Garavito, Ignacio Aldana, Silvia Galiano
Design, synthesis, structure-activity relationship, cytotoxicity studies, in silico drug-likeness, genotoxicity screening, and in vivo studies of new 1-aryl-3-substituted propanol derivatives led to the identification of nine compounds with promising in vitro (55, 56, 61, 64, 66, and 70-73) and in vivo (66 and 72) antimalarial profiles against Plasmodium falciparum and Plasmodium berghei. Compounds 55, 56, 61, 64, 66 and 70-73 exhibited potent antiplasmodial activity against chloroquine-resistant strain FCR-3 (IC50 s < 0...
April 24, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29743474/a-comprehensive-model-for-assessment-of-liver-stage-therapies-targeting-plasmodium-vivax-and-plasmodium-falciparum
#16
Alison Roth, Steven P Maher, Amy J Conway, Ratawan Ubalee, Victor Chaumeau, Chiara Andolina, Stephen A Kaba, Amélie Vantaux, Malina A Bakowski, Richard Thomson Luque, Swamy Rakesh Adapa, Naresh Singh, Samantha J Barnes, Caitlin A Cooper, Mélanie Rouillier, Case W McNamara, Sebastian A Mikolajczak, Noah Sather, Benoît Witkowski, Brice Campo, Stefan H I Kappe, David E Lanar, François Nosten, Silas Davidson, Rays H Y Jiang, Dennis E Kyle, John H Adams
Malaria liver stages represent an ideal therapeutic target with a bottleneck in parasite load and reduced clinical symptoms; however, current in vitro pre-erythrocytic (PE) models for Plasmodium vivax and P. falciparum lack the efficiency necessary for rapid identification and effective evaluation of new vaccines and drugs, especially targeting late liver-stage development and hypnozoites. Herein we report the development of a 384-well plate culture system using commercially available materials, including cryopreserved primary human hepatocytes...
May 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29741228/sle-patients-show-an-increased-arterial-stiffness-that-is-predicted-by-igm-anti-%C3%A3-2-glycoprotein-i-and-small-dense-hdl-particles
#17
Sandra Parra, Miguel Lopez-Dupla, Daiana Ibarretxe, Mercedes de Las Heras, Nuria Amigó, Alba Català, Marc Benavent, Esperanza Garcés, Alvaro Navarro, Antoni Castro
BACKGROUND: Patients with systemic lupus erythematous (SLE) show increased cardiovascular mortality and morbidity. The accelerated atherosclerosis observed in SLE patients has been measured by the carotid intima media thickness (c-IMT) and functional vascular tests, such as the arterial stiffness that occurs before plaque formation. AIMS: To investigate the metabolic and immunological factors associated with the presence of central arterial stiffness measured by the augmentation index (AIx)...
May 9, 2018: Arthritis Care & Research
https://www.readbyqxmd.com/read/29741150/comparison-of-the-pharmacokinetics-and-ex-vivo-antimalarial-activities-of-artesunate-amodiaquine-and-artemisinin-piperaquine-in-healthy-volunteers-for-preselection-malaria-therapy
#18
Nguyen Ngoc Quang, Marina Chavchich, Chu Xuan Anh, Geoffrey W Birrell, Karin van Breda, Thomas Travers, Kerryn Rowcliffe, Michael D Edstein
The pharmacokinetics (PK) and ex vivo activity (pharmacodynamics [PD]) of two artemisinin combination therapies (ACTs) (artemisinin-piperaquine [ARN-PPQ] [Artequick® ] and artesunate-amodiaquine [ARS-AQ] [Coarsucam™ ]) in healthy Vietnamese volunteers were compared following 3-day courses of the ACTs for the preselection of the drugs for falciparum malaria therapy. For PK analysis, serial plasma samples were collected from two separate groups of 22 volunteers after ACT administration. Of these volunteers, ex vivo activity was assessed in plasma samples from seven volunteers who received both ACTs...
May 7, 2018: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29739907/clag3-self-associates-in-malaria-parasites-and-quantitatively-determines-nutrient-uptake-channels-at-the-host-membrane
#19
Ankit Gupta, Praveen Balabaskaran-Nina, Wang Nguitragool, Gagandeep S Saggu, Marc A Schureck, Sanjay A Desai
Malaria parasites increase host erythrocyte permeability to ions and nutrients via a broad-selectivity channel known as the plasmodial surface anion channel (PSAC), linked to parasite-encoded CLAG3 and two associated proteins. These proteins lack the multiple transmembrane domains typically present in channel-forming proteins, raising doubts about their precise roles. Using the virulent human Plasmodium falciparum parasite, we report that CLAG3 undergoes self-association and that this protein's expression determines channel phenotype quantitatively...
May 8, 2018: MBio
https://www.readbyqxmd.com/read/29737894/a-systems-biology-approach-to-antimalarial-drug-discovery
#20
Wilian Augusto Cortopassi, Tanos Celmar Costa Franca, Antoniana Ursine Krettli
In spite of significant efforts to reduce malaria deaths, this disease still kills around 445,000 people every year. Overcoming drug resistance is one of the main goals of current malaria research programs. This is challenging, since the biology of Plasmodium is not fully understood, requiring the development of advanced models for data analysis in the search for new antimalarials. Areas covered: In this review the authors introduce the importance of computational models to address the challenges of drug discovery, presenting examples of pioneering systems biology approaches in the search for new antimalarial drugs and their role in the future of drug research programs...
May 8, 2018: Expert Opinion on Drug Discovery
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