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https://www.readbyqxmd.com/read/28542423/plasmid-free-crispr-cas9-genome-editing-in-plasmodium-falciparum-confirms-mutations-conferring-resistance-to-the-dihydroisoquinolone-clinical-candidate-sj733
#1
Emily D Crawford, Jenai Quan, Jeremy A Horst, Daniel Ebert, Wesley Wu, Joseph L DeRisi
Genetic manipulation of the deadly malaria parasite Plasmodium falciparum remains challenging, but the rise of CRISPR/Cas9-based genome editing tools is increasing the feasibility of altering this parasite's genome in order to study its biology. Of particular interest is the investigation of drug targets and drug resistance mechanisms, which have major implications for fighting malaria. We present a new method for introducing drug resistance mutations in P. falciparum without the use of plasmids or the need for cloning homologous recombination templates...
2017: PloS One
https://www.readbyqxmd.com/read/28542335/interventions-that-effectively-target-anopheles-funestus-mosquitoes-could-significantly-improve-control-of-persistent-malaria-transmission-in-south-eastern-tanzania
#2
Emmanuel W Kaindoa, Nancy S Matowo, Halfan S Ngowo, Gustav Mkandawile, Arnold Mmbando, Marcelina Finda, Fredros O Okumu
Malaria is transmitted by many Anopheles species whose proportionate contributions vary across settings. We re-assessed the roles of Anopheles arabiensis and Anopheles funestus, and examined potential benefits of species-specific interventions in an area in south-eastern Tanzania, where malaria transmission persists, four years after mass distribution of long-lasting insecticide-treated nets (LLINs). Monthly mosquito sampling was done in randomly selected households in three villages using CDC light traps and back-pack aspirators, between January-2015 and January-2016, four years after the last mass distribution of LLINs in 2011...
2017: PloS One
https://www.readbyqxmd.com/read/28542123/malaria-surveillance-united-states-2014
#3
Kimberly E Mace, Paul M Arguin
PROBLEM/CONDITION: Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles mosquito. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. However, malaria is occasionally acquired by persons who have not traveled out of the country through exposure to infected blood products, congenital transmission, laboratory exposure, or local mosquitoborne transmission...
May 26, 2017: MMWR. Surveillance Summaries: Morbidity and Mortality Weekly Report. Surveillance Summaries
https://www.readbyqxmd.com/read/28539634/the-plasmodium-pi-4-k-inhibitor-kdu691-selectively-inhibits-dihydroartemisinin-pretreated-plasmodium-falciparum-ring-stage-parasites
#4
L Dembele, X Ang, M Chavchich, G M C Bonamy, J J Selva, M Yi-Xiu Lim, C Bodenreider, B K S Yeung, F Nosten, B M Russell, M D Edstein, J Straimer, D A Fidock, T T Diagana, P Bifani
Malaria control and elimination are threatened by the emergence and spread of resistance to artemisinin-based combination therapies (ACTs). Experimental evidence suggests that when an artemisinin (ART)-sensitive (K13 wild-type) Plasmodium falciparum strain is exposed to ART derivatives such as dihydroartemisinin (DHA), a small population of the early ring-stage parasites can survive drug treatment by entering cell cycle arrest or dormancy. After drug removal, these parasites can resume growth. Dormancy has been hypothesized to be an adaptive physiological mechanism that has been linked to recrudescence of parasites after monotherapy with ART and, possibly contributes to ART resistance...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539125/do-anti-malarials-in-africa-meet-quality-standards-the-market-penetration-of-non-quality-assured-artemisinin-combination-therapy-in-eight-african-countries
#5
Paul N Newton, Kara Hanson, Catherine Goodman
BACKGROUND: Quality of artemisinin-based combination therapy (ACT) is important for ensuring malaria parasite clearance and protecting the efficacy of artemisinin-based therapies. The extent to which non quality-assured ACT (non-QAACT), or those not granted global regulatory approval, are available and used to treat malaria in endemic countries is poorly documented. This paper uses national and sub-national medicine outlet surveys conducted in eight study countries (Benin, Kinshasa and Kantanga [Democratic Republic of the Congo, DRC], Kenya, Madagascar, Nigeria, Tanzania, Uganda and Zambia) between 2009 and 2015 to describe the non-QAACT market and to document trends in availability and distribution of non-QAACT in the public and private sector...
May 25, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28537265/a-tetraoxane-based-antimalarial-drug-candidate-that-overcomes-pfk13-c580y-dependent-artemisinin-resistance
#6
Paul M O'Neill, Richard K Amewu, Susan A Charman, Sunil Sabbani, Nina F Gnädig, Judith Straimer, David A Fidock, Emma R Shore, Natalie L Roberts, Michael H-L Wong, W David Hong, Chandrakala Pidathala, Chris Riley, Ben Murphy, Ghaith Aljayyoussi, Francisco Javier Gamo, Laura Sanz, Janneth Rodrigues, Carolina Gonzalez Cortes, Esperanza Herreros, Iñigo Angulo-Barturén, María Belén Jiménez-Díaz, Santiago Ferrer Bazaga, María Santos Martínez-Martínez, Brice Campo, Raman Sharma, Eileen Ryan, David M Shackleford, Simon Campbell, Dennis A Smith, Grennady Wirjanata, Rintis Noviyanti, Ric N Price, Jutta Marfurt, Michael J Palmer, Ian M Copple, Amy E Mercer, Andrea Ruecker, Michael J Delves, Robert E Sinden, Peter Siegl, Jill Davies, Rosemary Rochford, Clemens H M Kocken, Anne-Marie Zeeman, Gemma L Nixon, Giancarlo A Biagini, Stephen A Ward
K13 gene mutations are a primary marker of artemisinin resistance in Plasmodium falciparum malaria that threatens the long-term clinical utility of artemisinin-based combination therapies, the cornerstone of modern day malaria treatment. Here we describe a multinational drug discovery programme that has delivered a synthetic tetraoxane-based molecule, E209, which meets key requirements of the Medicines for Malaria Venture drug candidate profiles. E209 has potent nanomolar inhibitory activity against multiple strains of P...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28535801/molecular-markers-of-anti-malarial-drug-resistance-in-central-west-and-east-african-children-with-severe-malaria
#7
Christian N Nguetse, Ayola Akim Adegnika, Tsiri Agbenyega, Bernhards R Ogutu, Sanjeev Krishna, Peter G Kremsner, Thirumalaisamy P Velavan
BACKGROUND: The Plasmodium falciparum multidrug resistance 1 (PfMDR1), P. falciparum Ca(2+)-ATPase (PfATP6) and Kelch-13 propeller domain (PfK13) loci are molecular markers of parasite susceptibility to anti-malarial drugs. Their frequency distributions were determined in the isolates collected from children with severe malaria originating from three African countries. METHODS: Samples from 287 children with severe malaria [(Gabon: n = 114); (Ghana: n = 89); (Kenya: n = 84)] were genotyped for pfmdr1, pfatp6 and pfk13 loci by DNA sequencing and assessing pfmdr1 copy number variation (CNV) by real-time PCR...
May 23, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28535797/within-host-selection-of-drug-resistance-in-a-mouse-model-of-repeated-interrupted-treatment-of-plasmodium-yoelii-infection
#8
Suci Nuralitha, Josephine E Siregar, Din Syafruddin, Andy I M Hoepelman, Sangkot Marzuki
BACKGROUND: To study within-host selection of resistant parasites, an important factor in the development of resistance to anti-malarial drugs, a mouse model of repeated interrupted malaria treatment (RIT) has been developed. The characteristics of within host selection of resistance to atovaquone and pyrimethamine in Plasmodium yoelii was examined in such a model. METHODS: Treatment of P. yoelii infected mice, with atovaquone or pyrimethamine, was started at parasitaemia level of 3-5%, interrupted when reduced to less than 0...
May 23, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28533790/aapdr3-a-pdr-transporter-3-is-involved-in-sesquiterpene-%C3%AE-caryophyllene-transport-in-artemisia-annua
#9
Xueqing Fu, Pu Shi, Qian He, Qian Shen, Yueli Tang, Qifang Pan, Yanan Ma, Tingxiang Yan, Minghui Chen, Xiaolong Hao, Pin Liu, Ling Li, Yuliang Wang, Xiaofen Sun, Kexuan Tang
Artemisinin, a sesquiterpenoid endoperoxide, isolated from the plant Artemisia annua L., is widely used in the treatment of malaria. Another sesquiterpenoid, β-caryophyllene having antibiotic, antioxidant, anticarcinogenic and local anesthetic activities, is also presented in A. annua. The role played by sesquiterpene transporters in trichomes and accumulation of these metabolites is poorly understood in A. annua and in trichomes of other plant species. We identified AaPDR3, encoding a pleiotropic drug resistance (PDR) transporter located to the plasma membrane from A...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28533179/polymorphisms-in-pfdhfr-and-pfdhps-genes-after-five-years-of-artemisinin-combination-therapy-act-implementation-from-urban-kolkata-india
#10
Moytrey Chatterjee, Swagata Ganguly, Pabitra Saha, Subhasish K Guha, Ardhendu Kumar Maji
BACKGROUND: In India, sulphadoxine-pyrimethamine (SP) is now in use as a partner drug of ACT (AS+SP) to treat uncomplicated falciparum malaria since 2010. Declined trend of AS+SP efficacy has been reported from north-eastern states of the country. It is not possible to determine the efficacy of SP alone from any study with ACT. So, this work was designed to study the pattern of polymorphisms in pfdhfr and pfdhps genes to predict the SP resistance status among parasite population of urban Kolkata after five years of ACT implementation...
May 19, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28531845/artesunate-and-erythropoietin-synergistically-improve-the-outcome-of-experimental-cerebral-malaria
#11
Yunting Du, Guang Chen, Xuexing Zhang, Chunyun Yu, Yaming Cao, Liwang Cui
Cerebral malaria (CM) is a severe neurological syndrome in humans and the main fatal cause of malaria. In malaria epidemic regions, despite appropriate anti-malarial treatment, 10-20% of deaths still occur during the acute phase. This is largely attributable to poor treatment access, therapeutic complexity and drug resistance; thus, developing additional clinical adjunctive therapies is an urgent necessity. In this study, we investigated the effect of artesunate (AST) and recombinant human erythropoietin (rhEPO) using an experimental cerebral malaria (ECM) model-C57BL/6 mice infected with Plasmodium berghei ANKA (PbA)...
May 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28531230/identifying-artemisinin-resistance-from-parasite-clearance-half-life-data-with-a-simple-shiny-web-application
#12
Sai Thein Than Tun, Yoel Lubell, Arjen M Dondorp, Tom Fieldman, Kyaw Myo Tun, Olivier Celhay, Xin Hui Chan, Sompob Saralamba, Lisa J White
The emergence of artemisinin-resistant Plasmodium falciparum malaria is a major threat to malaria elimination. New tools for supporting the surveillance of artemisinin resistance are critical for current and future malaria control and elimination strategies. We have developed an open-access, user-friendly, web-based tool to analyse parasite clearance half-life data of P. falciparum infected patients after treatment with artemisinin derivatives, so that resistance to artemisinin can be identified. The tool can be accessed at bit...
2017: PloS One
https://www.readbyqxmd.com/read/28526047/the-paradigm-of-eave-tubes-scaling-up-house-improvement-and-optimizing-insecticide-delivery-against-disease-transmitting-mosquitoes
#13
Fredros Okumu
Control of mosquito-borne diseases is greatly compromised by spread of insecticide resistance, high implementation costs and sub-optimal compliance among users. Improved housing has potential to reduce malaria transmission nearly as much as long-lasting insecticide-treated nets (LLINs), while also preventing other arthropod-borne diseases and improving overall well-being. Yet, it is hardly promoted as mainstream intervention, partly because of high costs, minimal communal benefits to people in non-improved houses, and low scalability...
May 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28522690/resistance-to-malaria-through-structural-variation-of-red-blood-cell-invasion-receptors
#14
Ellen M Leffler, Gavin Band, George B J Busby, Katja Kivinen, Quang Si Le, Geraldine M Clarke, Kalifa A Bojang, David J Conway, Muminatou Jallow, Fatoumatta Sisay-Joof, Edith C Bougouma, Valentina D Mangano, David Modiano, Sodiomon B Sirima, Eric Achidi, Tobias O Apinjoh, Kevin Marsh, Carolyne M Ndila, Norbert Peshu, Thomas N Williams, Chris Drakeley, Alphaxard Manjurano, Hugh Reyburn, Eleanor Riley, David Kachala, Malcolm Molyneux, Vysaul Nyirongo, Terrie Taylor, Nicole Thornton, Louise Tilley, Shane Grimsley, Eleanor Drury, Jim Stalker, Victoria Cornelius, Christina Hubbart, Anna E Jeffreys, Kate Rowlands, Kirk A Rockett, Chris C A Spencer, Dominic P Kwiatkowski
The malaria parasite Plasmodium falciparum invades human red blood cells via interactions between host and parasite surface proteins. By analyzing genome sequence data from human populations, including 1269 individuals from sub-Saharan Africa, we identify a diverse array of large copy number variants affecting the host invasion receptor genes GYPA and GYPB We find that a nearby association with severe malaria is explained by a complex structural rearrangement involving the loss of GYPB and gain of two GYPB-A hybrid genes, which encode a serologically distinct blood group antigen known as Dantu...
May 18, 2017: Science
https://www.readbyqxmd.com/read/28521791/exploring-the-role-of-socioeconomic-factors-in-the-development-and-spread-of-anti-malarial-drug-resistance-a-qualitative-study
#15
Philip Emeka Anyanwu, John Fulton, Etta Evans, Timothy Paget
BACKGROUND: Malaria remains a global health issue with the burden unevenly distributed to the disadvantage of the developing countries of the world. Poverty contributes to the malaria burden as it has the ability to affect integral aspects of malaria control. There have been renewed efforts in the global malaria control, resulting in reductions in the global malaria burden over the last decade. However, the development of resistance to artemisinin-based combination therapy threatens the sustainability of the present success in malaria control...
May 18, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28511659/antiplasmodial-activity-of-indigofera-spicata-root-extract-against-plasmodium-berghei-infection-in-mice
#16
Eshetie Melese Birru, Mestayet Geta, Abyot Endale Gurmu
BACKGROUND: In addition to pharmacovigilance and pharmaco-economic concerns, resistance to anti-malarial medicines has been documented in all classes of anti-malarials and this is further worsened by resistance to common insecticides by malaria vector, which is a major threat to malaria control. As a means of facing the challenges of searching for new anti-malarial agents, the current study focused on evaluation of anti-malarial activity of root extract of Indigofera spicata. METHODS: Chloroquine-sensitive rodent malaria parasite, Plasmodium berghei (ANKA strain) was used to infect the Swiss Albino mice in 4-day suppressive and curative models...
May 16, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28511056/elimination-of-schistosoma-mansoni-in-infected-mice-by-slow-release-of-artemisone
#17
Daniel Gold, Mohammed Alian, Avraham Domb, Yara Karawani, Maysa Jbarien, Jacques Chollet, Richard K Haynes, Ho Ning Wong, Viola Buchholz, Andreas Greiner, Jacob Golenser
The current treatment of schistosomiasis is based on the anti-helminthic drug praziquantel (PZQ). PZQ affects only the adult stages of schistosomes. In addition, resistance to PZQ is emerging. We suggest a drug, which could serve as a potential alternative or complement to PZQ, and as a means of treating infections at earlier, pre-granuloma stage. Derivatives of the peroxidic antimalarial drug artemisinin have been indicated as alternatives, because both plasmodia and schistosomes are blood-feeding parasites...
May 4, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28510573/comparison-of-artemether-lumefantrine-and-chloroquine-with-and-without-primaquine-for-the-treatment-of-plasmodium-vivax-infection-in-ethiopia-a-randomized-controlled-trial
#18
Tesfay Abreha, Jimee Hwang, Kamala Thriemer, Yehualashet Tadesse, Samuel Girma, Zenebe Melaku, Ashenafi Assef, Moges Kassa, Mark D Chatfield, Keren Z Landman, Stella M Chenet, Naomi W Lucchi, Venkatachalam Udhayakumar, Zhiyong Zhou, Ya Ping Shi, S Patrick Kachur, Daddi Jima, Amha Kebede, Hiwot Solomon, Addis Mekasha, Bereket Hailegiorgis Alemayehu, Joseph L Malone, Gunewardena Dissanayake, Hiwot Teka, Sarah Auburn, Lorenz von Seidlein, Ric N Price
BACKGROUND: Recent efforts in malaria control have resulted in great gains in reducing the burden of Plasmodium falciparum, but P. vivax has been more refractory. Its ability to form dormant liver stages confounds control and elimination efforts. To compare the efficacy and safety of primaquine regimens for radical cure, we undertook a randomized controlled trial in Ethiopia. METHODS AND FINDINGS: Patients with normal glucose-6-phosphate dehydrogenase status with symptomatic P...
May 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28507198/modern-vector-control
#19
Neil F Lobo, Nicole L Achee, John Greico, Frank H Collins
The rapid spread of mosquito resistance to currently available insecticides, and the current lack of an efficacious malaria vaccine are among many challenges that affect large-scale efforts for malaria control. As goals of malaria elimination and eradication are put forth, new vector-control paradigms and tools and/or further optimization of current vector-control products are required to meet public health demands. Vector control remains the most effective measure to prevent malaria transmission and present gains against malaria mortality and morbidity may be maintained as long as vector-intervention strategies are sustained and adapted to underlying vector-related transmission dynamics...
May 15, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28507193/current-and-future-prospects-for-preventing-malaria-transmission-via-the-use-of-insecticides
#20
Hilary Ranson
Malaria vectors have developed resistance to all classes of insecticides that are used to target the adult mosquito to prevent parasite transmission. The number of resistant mosquito populations has increased dramatically in recent years, most likely as a result of the scale-up of vector control activities, and the intensity of this resistance is increasing rapidly and compromising the performance of vector control tools. Bednets and indoor residual spray formulations containing alternative active ingredients have shown promise in field trials but are still several years away from implementation...
May 15, 2017: Cold Spring Harbor Perspectives in Medicine
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