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https://www.readbyqxmd.com/read/29346647/resistance-to-selected-pyrethroid-insecticides-in-the-malaria-mosquito-anopheles-stephensi-diptera-muscidae-from-punjab-pakistan
#1
Hafiz Azhar Ali Khan, Waseem Akram, Sumi Lee
Pyrethroids are commonly used insecticides in malaria control programs; however, insecticide resistance limits the benefits gained by using these insecticides. In the present study, we assessed the resistance status for different pyrethroids of the malaria mosquito vector, Anopheles stephensi Liston (Diptera: Muscidae), in the Punjab province, Pakistan. Bioassays were conducted using diagnostic doses following standard World Health Organization protocols: 0.05% λ-cyhalothrin, 0.75% permethrin, 0.15% cyfluthrin, 0...
January 16, 2018: Journal of Medical Entomology
https://www.readbyqxmd.com/read/29345221/therapeutic-response-to-dihydroartemisinin-piperaquine-for-p-falciparum-and-p-vivax-nine-years-after-its-introduction-in-southern-papua-indonesia
#2
Jeanne Rini Poespoprodjo, Enny Kenangalem, Johny Wafom, Freis Chandrawati, Agatha M Puspitasari, Benedikt Ley, Leily Trianti, Zoé Korten, Asik Surya, Din Syafruddin, Nicholas M Anstey, Jutta Marfurt, Rintis Noviyanti, Ric N Price
Dihydroartemisinin-piperaquine (DHP) has been the first-line treatment of uncomplicated malaria due to both Plasmodium falciparum and Plasmodium vivax infections in Papua, Indonesia, since March 2006. The efficacy of DHP was reassessed to determine whether there had been any decline following almost a decade of its extensive use. An open-label drug efficacy study of DHP for uncomplicated P. falciparum and P. vivax malaria was carried out between March 2015 and April 2016 in Timika, Papua, Indonesia. Patients with uncomplicated malaria were administered supervised DHP tablets once daily for 3 days...
January 15, 2018: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29343745/malaria-infected-red-blood-cells-release-small-regulatory-rnas-through-extracellular-vesicles
#3
Kehinde Adebayo Babatunde, Smart Mbagwu, María Andrea Hernández-Castañeda, Swamy R Adapa, Michael Walch, Luis Filgueira, Laurent Falquet, Rays H Y Jiang, Ionita Ghiran, Pierre-Yves Mantel
The parasite Plasmodium falciparum causes the most severe form of malaria. Cell communication between parasites is an important mechanism to control population density and differentiation. The infected red blood cells (iRBCs) release small extracellular vesicles (EVs) that transfer cargoes between cells. The EVs synchronize the differentiation of the asexual parasites into gametocytes to initiate the transmission to the mosquito. Beside their role in parasite communication, EVs regulate vascular function. So far, the exact cargoes responsible for cellular communication remain unknown...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29342187/induction-of-high-tolerance-to-artemisinin-by-sub-lethal-administration-a-new-in-vitro-model-of-p-falciparum
#4
Serena De Lucia, Ioannis Tsamesidis, Maria Carmina Pau, Kristina R Kesely, Antonella Pantaleo, Francesco Turrini
Artemisinin resistance is a major threat to malaria control efforts. Resistance is characterized by an increase in the Plasmodium falciparum parasite clearance half-life following treatment with artemisinin-based combination therapies (ACTs) and an increase in the percentage of surviving parasites. The remarkably short blood half-life of artemisinin derivatives may contribute to drug-resistance, possibly through factors including sub-lethal plasma concentrations and inadequate exposure. Here we selected for a new strain of artemisinin resistant parasites, termed the artemisinin resistant strain 1 (ARS1), by treating P...
2018: PloS One
https://www.readbyqxmd.com/read/29339390/identification-of-hsp90-inhibitors-with-anti-plasmodium-activity
#5
Dora Posfai, Amber L Eubanks, Allison I Keim, Kuan-Yi Lu, Grace Z Wang, Philip F Hughes, Nobutaka Kato, Timothy A Haystead, Emily R Derbyshire
Malaria remains a global health burden partly due to Plasmodium parasite resistance to first-line therapeutics. The molecular chaperone heat shock protein 90 (Hsp90) has emerged as an essential protein for blood stage Plasmodium parasites, but details about its function during malaria's elusive liver stage are unclear. We used target-based screens to identify compounds that bind to Plasmodium falciparum and human Hsp90, which revealed insights into chemotypes with species selective binding. Using cell-based malaria assays, we demonstrate that all identified Hsp90-binding compounds are liver and blood stage Plasmodium inhibitors...
January 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29335000/molecular-characterization-of-babesia-microti-thioredoxin-bmtrx2-and-its-expression-patterns-induced-by-antiprotozoal-drugs
#6
Jingwei Huang, Kang Xiong, Houshuang Zhang, Yanzhen Zhao, Jie Cao, Haiyan Gong, Yongzhi Zhou, Jinlin Zhou
BACKGROUND: Human babesiosis is an infectious disease that is epidemic in various regions all over the world. The predominant causative pathogen of this disease is the intra-erythrocytic parasite Babesia microti. The thioredoxin system is one of the major weapons that is used in the resistance to the reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced by host immune system. In other intra-erythrocytic apicomplexans like the malaria parasite Plasmodium falciparum, anti-oxidative proteins are promising targets for the development of anti-parasitic drugs...
January 15, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29334942/poor-response-to-artesunate-treatment-in-two-patients-with-severe-malaria-on-the-thai-myanmar-border
#7
Aung Pyae Phyo, Kyaw Kyaw Win, Aung Myint Thu, Lei Lei Swe, Htike Htike, Candy Beau, Kanlaya Sriprawat, Markus Winterberg, Stephane Proux, Mallika Imwong, Elizabeth A Ashley, Francois Nosten
BACKGROUND: Malaria has declined dramatically along the Thai-Myanmar border in recent years due to malaria control and elimination programmes. However, at the same time, artemisinin resistance has spread, raising concerns about the efficacy of parenteral artesunate for the treatment of severe malaria. CASE PRESENTATION: In November 2015 and April 2017, two patients were treated for severe malaria with parenteral artesunate. Quinine was added within 24 h due to an initial poor response to treatment...
January 15, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29334758/anticancer-thiosemicarbazones-chemical-properties-interaction-with-iron-metabolism-and-resistance-development
#8
Petra Heffeter, Veronika F S Pape, Eva A Enyedy, Bernhard K Keppler, Gergely Szakas, Christian R Kowol
SIGNIFICANCE: During the last decades, thiosemicarbazones have been clinically developed for a variety of diseases including tuberculosis, viral infections, malaria and cancer. With regard to malignant diseases, the class of α-N-heterocyclic thiosemicarbazones, and here especially Triapine, was intensively developed in multiple clinical phase I/II trials. Recent Advances: Very recently two new derivatives, namely COTI-2 and DpC have entered phase I evaluation. Based on the strong metal-chelating/metal-interacting properties of thiosemicarbazones, interference with the cellular iron (and copper) homeostasis is assumed to play an important role in their biological activity...
January 15, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29332383/developing-pantetheinase-resistant-pantothenamide-antibacterials-structural-modification-impacts-on-pank-interaction-and-mode-of-action
#9
Leanne Barnard, Konrad Johannes Mostert, Willem A L van Otterlo, Erick Strauss
Pantothenamides (PanAms) are analogues of pantothenate, the biosynthetic precursor of coenzyme A (CoA), and show potent antimicrobial activity against several bacteria and the malaria parasite in vitro. However, pantetheinase enzymes that normally degrade pantetheine in human serum also act on the PanAms, thereby reducing their potency. In this study, we designed analogues of the known antibacterial PanAm N-heptylpantothenamide (N7-Pan) to be resistant to pantetheinase by using three complementary structural modification strategies...
January 14, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29332155/prevalence-of-the-pfdhfr-and-pfdhps-mutations-among-asymptomatic-pregnant-women-in-southeast-nigeria
#10
Ekpereonne Esu, Costanza Tacoli, Prabhanjan Gai, Nicole Berens-Riha, Michael Pritsch, Thomas Loescher, Martin Meremikwu
Sulfadoxine-pyrimethamine (SP) is the recommended drug for intermittent preventive treatment of malaria in pregnancy in most of sub-Saharan Africa. Resistance to SP is related to mutations in the dhfr and dhps gene of Plasmodium falciparum. This study determined the prevalence of Pfdhfr and Pfdhps polymorphisms found in asymptomatic pregnant women attending antenatal care in Calabar, Nigeria. From October 2013 to November 2014, asymptomatic pregnant women attending antenatal care clinics were enrolled after obtaining informed consent...
January 13, 2018: Parasitology Research
https://www.readbyqxmd.com/read/29330980/comparison-of-efficacy-of-chloroquine-and-artemether-lumafantrine-in-treating-vivax-malaria-in-thall-and-surrounding-area
#11
Syed Mohammad Abrar, Syed Sajid Ali Shah, Raja Jibran Akbar, Sheema Rahim, Faizan Malik, Fakhar Uzzaman Khan
BACKGROUND: Fever is the main complaint in patients reporting to our hospital and the most common cause of fever in our set up is malaria. The aim of this study was to know about the clinical response, efficacy and resistance of vivax malaria to chloroquine in patients reporting to Thall Scouts Hospital. METHODS: All the adult male patients reporting to Thall Scouts Hospital with fever and other symptoms of malaria having slide positive vivax malaria were included in the study...
October 2017: Journal of Ayub Medical College, Abbottabad: JAMC
https://www.readbyqxmd.com/read/29329545/use-of-epidemiological-and-entomological-tools-in-the-control-and-elimination-of-malaria-in-ethiopia
#12
REVIEW
Abebe Animut, Bernt Lindtjørn
Malaria is the leading public health problem in Ethiopia where over 75% of the land surface is at risk with varying intensities depending on altitude and season. Although the mortality because of malaria infection has declined much during the last 15-20 years, some researchers worry that this success story may not be sustainable. Past notable achievements in the reduction of malaria disease burden could be reversed in the future. To interrupt, or even to eliminate malaria transmission in Ethiopia, there is a need to implement a wide range of interventions that include insecticide-treated bed nets, indoor residual spraying, improved control of residual malaria transmission, and improved diagnostics, enhanced surveillance, and methods to deal with the emergence of resistance both to drugs and to insecticides...
January 12, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29327915/multispectral-atomic-force-microscopy-infrared-nano-imaging-of-malaria-infected-red-blood-cells
#13
David Perez-Guaita, Kamila Kochan, Mitchell Batty, Christian Doerig, Jose Garcia-Bustos, Shirley Josefina Espinoza Herrera, Don McNaughton, Philip Heraud, Bayden R Wood
Atomic Force Microscopy-Infrared (AFM-IR) spectroscopy is a powerful new technique that can be applied to study molecular composition of cells and tissues at the nano-scale. AFM-IR maps are acquired using single wavenumber value: they show either the absorbance plotted against a single wavenumber value, or a ratio of two absorbance values. Here we implement multivariate image analysis to generate multivariate AFM-IR maps, and use this approach to resolve subcellular structural information in red blood cells infected with Plasmodium falciparum at different stages of development...
January 12, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29326268/mapping-the-malaria-parasite-druggable-genome-by-using-in-vitro-evolution-and-chemogenomics
#14
Annie N Cowell, Eva S Istvan, Amanda K Lukens, Maria G Gomez-Lorenzo, Manu Vanaerschot, Tomoyo Sakata-Kato, Erika L Flannery, Pamela Magistrado, Edward Owen, Matthew Abraham, Gregory LaMonte, Heather J Painter, Roy M Williams, Virginia Franco, Maria Linares, Ignacio Arriaga, Selina Bopp, Victoria C Corey, Nina F Gnädig, Olivia Coburn-Flynn, Christin Reimer, Purva Gupta, James M Murithi, Pedro A Moura, Olivia Fuchs, Erika Sasaki, Sang W Kim, Christine H Teng, Lawrence T Wang, Aslı Akidil, Sophie Adjalley, Paul A Willis, Dionicio Siegel, Olga Tanaseichuk, Yang Zhong, Yingyao Zhou, Manuel Llinás, Sabine Ottilie, Francisco-Javier Gamo, Marcus C S Lee, Daniel E Goldberg, David A Fidock, Dyann F Wirth, Elizabeth A Winzeler
Chemogenetic characterization through in vitro evolution combined with whole-genome analysis can identify antimalarial drug targets and drug-resistance genes. We performed a genome analysis of 262 Plasmodium falciparum parasites resistant to 37 diverse compounds. We found 159 gene amplifications and 148 nonsynonymous changes in 83 genes associated with drug-resistance acquisition, where gene amplifications contributed to one-third of resistance acquisition events. Beyond confirming previously identified multidrug-resistance mechanisms, we discovered hitherto unrecognized drug target-inhibitor pairs, including thymidylate synthase and a benzoquinazolinone, farnesyltransferase and a pyrimidinedione, and a dipeptidylpeptidase and an arylurea...
January 12, 2018: Science
https://www.readbyqxmd.com/read/29321371/assessing-drug-efficacy-against-plasmodium-falciparum-liver-stages-in-vivo
#15
Erika L Flannery, Lander Foquet, Vorada Chuenchob, Matthew Fishbaugher, Zachary Billman, Mary Jane Navarro, William Betz, Tayla M Olsen, Joshua Lee, Nelly Camargo, Thao Nguyen, Carola Schafer, Brandon K Sack, Elizabeth M Wilson, Jessica Saunders, John Bial, Brice Campo, Susan A Charman, Sean C Murphy, Margaret A Phillips, Stefan Hi Kappe, Sebastian A Mikolajczak
Malaria eradication necessitates new tools to fight the evolving and complex Plasmodium pathogens. These tools include prophylactic drugs that eliminate Plasmodium liver stages and consequently prevent clinical disease, decrease transmission, and reduce the propensity for resistance development. Currently, the identification of these drugs relies on in vitro P. falciparum liver stage assays or in vivo causal prophylaxis assays using rodent malaria parasites; there is no method to directly test in vivo liver stage activity of candidate antimalarials against the human malaria-causing parasite P...
January 11, 2018: JCI Insight
https://www.readbyqxmd.com/read/29321052/asgdb-a-specialised-genomic-resource-for-interpreting-anopheles-sinensis-insecticide%C3%A2-resistance
#16
Dan Zhou, Yang Xu, Cheng Zhang, Meng-Xue Hu, Yun Huang, Yan Sun, Lei Ma, Bo Shen, Chang-Liang Zhu
BACKGROUND: Anopheles sinensis is an important malaria vector in Southeast Asia. The widespread emergence of insecticide resistance in this mosquito species poses a serious threat to the efficacy of malaria control measures, particularly in China. Recently, the whole-genome sequencing and de novo assembly of An. sinensis (China strain) has been finished. A series of insecticide-resistant studies in An. sinensis have also been reported. There is a growing need to integrate these valuable data to provide a comprehensive database for further studies on insecticide-resistant management of An...
January 10, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29320160/efforts-aimed-to-reduce-attrition-in-antimalarial-drug-discovery-a-systematic-evaluation-of-current-antimalarial-targets-portfolio
#17
María Jesus Chaparro, Felix Calderon, Pablo Castañeda, Elena Fernandez Alvaro, Raquel Gabarro, Francisco-Javier Gamo, María G Gómez-Lorenzo, Julio Martín, Esther Fernandez
Malaria remains a major global health problem. In 2015 alone, more than 200 million cases of malaria were reported, and more than 400,000 deaths occurred. Since 2010, emerging resistance to current front-line ACTs (Artemisinin Combination Therapies) has been detected in endemic countries. Therefore, there is an urgency for new therapies based on novel modes of action, able to relieve symptoms as fast as the artemisinins and/or block malaria transmission. During the past few years, the antimalarial community has focused their efforts on phenotypic screening as a pragmatic approach to identify new hits...
January 10, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29319338/vigilance-and-sentinels-in-global-health-security
#18
Chris Lyttleton
Global health security is increasingly reliant on vigilance to provide early warning of transnational health threats. In theory, this approach requires that sentinels, based in communities most affected by new or re-emerging infectious diseases, deliver timely alerts of incipient risk. Medicalizing global safety also implies there are particular forms of insecurity that must be remedied to pre-empt disease spread. I examine vigilance in the context of spreading drug resistant malaria in Southeast Asian border zones and argue that to act as sentinels, marginal groups vulnerable to infection must be able to articulate what social and behavioral factors prompt proliferating disease risks...
January 10, 2018: Medical Anthropology
https://www.readbyqxmd.com/read/29317740/increased-susceptibility-to-plasmodium-falciparum-in-infants-is-associated-with-low-not-high-placental-malaria-parasitemia
#19
Samuel Tassi Yunga, Genevieve G Fouda, Grace Sama, Julia B Ngu, Rose G F Leke, Diane W Taylor
Risk of malaria in infants can be influenced by prenatal factors. In this study, the potential for placental parasitemia at delivery in predicting susceptibility of infants to Plasmodium falciparum (Pf) infections was evaluated. Seventy-two newborns of mothers who were placental malaria negative (PM-) and of mothers who were PM+ with below (PM+ Lo) and above (PM + Hi) median placental parasitemia, were actively monitored during their first year of life. Median time to first PCR-detected Pf infection was shorter in PM + Lo infants (2...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29317166/synthesis-in-vitro-antimalarial-activities-and-cytotoxicities-of-amino-artemisinin-ferrocene-derivatives
#20
Christo de Lange, Dina Coertzen, Frans J Smit, Johannes F Wentzel, Ho Ning Wong, Lyn-Marie Birkholtz, Richard K Haynes, David D N'Da
Novel derivatives bearing a ferrocene attached via a piperazine linker to C-10 of the artemisinin nucleus were prepared from dihydroartemisinin and screened against chloroquine (CQ) sensitive NF54 and CQ resistant K1 and W2 strains of Plasmodium falciparum (Pf) parasites. The overall aim is to imprint oxidant (from the artemisinin) and redox (from the ferrocene) activities. In a preliminary assessment, these compounds were shown to possess activities in the low nM range with the most active being compound 6 with IC50 values of 2...
December 26, 2017: Bioorganic & Medicinal Chemistry Letters
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