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Malaria drug resistance

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https://www.readbyqxmd.com/read/28232818/genome-wide-in-silico-analysis-of-the-mismatch-repair-components-of-plasmodium-falciparum-and-their-comparison-with-human-host
#1
Mohammed Tarique, Moaz Ahmad, Manish Chauhan, Renu Tuteja
Malaria a major parasitic infection globally particularly in tropical and sub-tropical regions of the world is responsible for about 198 million cases and estimated deaths due to this disease are about 0.6 million. The emergence of drug resistance in the malaria parasite is alarming and it is necessary to understand its underlying cause and molecular mechanisms. It has been established that drug resistant malaria parasites have defective mismatch repair (MMR) therefore it is essential to study this pathway and its components in detail...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28231817/malaria-parasite-clearance
#2
REVIEW
Nicholas J White
Following anti-malarial drug treatment asexual malaria parasite killing and clearance appear to be first order processes. Damaged malaria parasites in circulating erythrocytes are removed from the circulation mainly by the spleen. Splenic clearance functions increase markedly in acute malaria. Either the entire infected erythrocytes are removed because of their reduced deformability or increased antibody binding or, for the artemisinins which act on young ring stage parasites, splenic pitting of drug-damaged parasites is an important mechanism of clearance...
February 23, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28230749/design-of-drug-delivery-systems-containing-artemisinin-and-its-derivatives
#3
REVIEW
Blessing Atim Aderibigbe
Artemisinin and its derivatives have been reported to be experimentally effective for the treatment of highly aggressive cancers without developing drug resistance, they are useful for the treatment of malaria, other protozoal infections and they exhibit antiviral activity. However, they are limited pharmacologically by their poor bioavailability, short half-life in vivo, poor water solubility and long term usage results in toxicity. They are also expensive for the treatment of malaria when compared to other antimalarials...
February 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28222727/developing-global-maps-of-insecticide-resistance-risk-to-improve-vector-control
#4
Michael Coleman, Janet Hemingway, Katherine Ann Gleave, Antoinette Wiebe, Peter W Gething, Catherine L Moyes
BACKGROUND: Significant reductions in malaria transmission have been achieved over the last 15 years with elimination occurring in a small number of countries, however, increasing drug and insecticide resistance threatens these gains. Insecticide resistance has decreased the observed mortality to the most commonly used insecticide class, the pyrethroids, and the number of alternative classes approved for use in public health is limited. Disease prevention and elimination relies on operational control of Anopheles malaria vectors, which requires the deployment of effective insecticides...
February 21, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28221121/molecular-evidence-of-drug-resistance-in-asymptomatic-malaria-infections-myanmar-2015
#5
Myat Htut Nyunt, Thinzar Shein, Ni Ni Zaw, Soe Soe Han, Fauzi Muh, Seong-Kyun Lee, Jin-Hee Han, Kyaw Zin Thant, Eun-Taek Han, Myat Phone Kyaw
Artemisinin resistance containment in Myanmar was initiated in 2011 after artemisinin-resistant Plasmodium falciparum malaria was reported. Molecular evidence suggests that asymptomatic malaria infections harboring drug resistance genes are present among residents of the Myanmar artemisinin resistance containment zone. This evidence supports efforts to eliminate these hidden infections.
March 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28219435/changing-the-policy-for-intermittent-preventive-treatment-with-sulfadoxine-pyrimethamine-during-pregnancy-in-malawi
#6
Chikondi A Mwendera, Christiaan de Jager, Herbert Longwe, Kamija Phiri, Charles Hongoro, Clifford M Mutero
BACKGROUND: The growing resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine (SP) treatment for uncomplicated malaria led to a recommendation by the World Health Organization for the use of artemisinin-based combination therapy. Inevitably, concerns were also raised surrounding the use of SP for intermittent prevention treatment of malaria during pregnancy (IPTp) amidst the lack of alternative drugs. Malawi was the first country to adopt intermittent prevention treatment with SP in 1993, and updated in 2013...
February 20, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28214367/population-genetic-structure-and-adaptation-of-malaria-parasites-on-the-edge-of-endemic-distribution
#7
Craig W Duffy, Hampate Ba, Samuel Assefa, Ambroise D Ahouidi, Yacine B Deh, Abderahmane Tandia, Freja C M Kirsebom, Dominic P Kwiatkowski, David J Conway
To determine whether the major human malaria parasite Plasmodium falciparum exhibits fragmented population structure or local adaptation at the northern limit of its African distribution where the dry Sahel zone meets the Sahara, samples were collected from diverse locations within Mauritania over a range of ~ 1000 kilometres. Microsatellite genotypes were obtained for 203 clinical infection samples from eight locations, and Illumina paired-end sequences were obtained to yield high coverage genome-wide single nucleotide polymorphism (SNP) data for 65 clinical infection samples from four locations...
February 18, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28213434/malaria-during-pregnancy
#8
Michal Fried, Patrick E Duffy
One hundred and twenty-five million women in malaria-endemic areas become pregnant each year (see Dellicour et al. PLoS Med7: e1000221 [2010]) and require protection from infection to avoid disease and death for themselves and their offspring. Chloroquine prophylaxis was once a safe approach to prevention but has been abandoned because of drug-resistant parasites, and intermittent presumptive treatment with sulfadoxine-pyrimethamine, which is currently used to protect pregnant women throughout Africa, is rapidly losing its benefits for the same reason...
February 17, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28212641/local-constraints-to-access-appropriate-malaria-treatment-in-the-context-of-parasite-resistance-in-cambodia-a-qualitative-study
#9
Jesse Verschuere, Tom Decroo, Dara Lim, Jean-Marie Kindermans, Chea Nguon, Rekol Huy, Yasmine Alkourdi, Koen Peeters Grietens, Charlotte Gryseels
BACKGROUND: Despite emerging drug resistance in Cambodia, artemisinin-based combination therapy (ACT) is still the most efficacious therapy. ACT is available free of charge in the Cambodian public sector and at a subsidized rate in the private sector. However, un- and mistreated cases in combination with population movements may lead to the further spread of resistant parasites, stressing the importance of understanding how the perceived aetiology of malaria and associated health-seeking behaviour may delay access to appropriate treatment...
February 17, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28212631/anti-malarial-effect-of-novel-chloroquine-derivatives-as-agents-for-the-treatment-of-malaria
#10
Seon-Ju Yeo, Dong-Xu Liu, Hak Sung Kim, Hyun Park
BACKGROUND: The widespread emergence of anti-malarial drug resistance has necessitated the discovery of novel anti-malarial drug candidates. In this study, chloroquine derivatives were evaluated for the improved anti-malarial activity. RESULTS: Novel two derivatives (SKM13 and SKM14) were synthesized based on the chloroquine (CQ) template containing modified side chains such as α,β-unsaturated amides and phenylmethyl group. The selective index indicated that SKM13 was 1...
February 17, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28199305/sterile-protection-against-human-malaria-by-chemoattenuated-pfspz-vaccine
#11
Benjamin Mordmüller, Güzin Surat, Heimo Lagler, Sumana Chakravarty, Andrew S Ishizuka, Albert Lalremruata, Markus Gmeiner, Joseph J Campo, Meral Esen, Adam J Ruben, Jana Held, Carlos Lamsfus Calle, Juliana B Mengue, Tamirat Gebru, Javier Ibáñez, Mihály Sulyok, Eric R James, Peter F Billingsley, K C Natasha, Anita Manoj, Tooba Murshedkar, Anusha Gunasekera, Abraham G Eappen, Tao Li, Richard E Stafford, Minglin Li, Phil L Felgner, Robert A Seder, Thomas L Richie, B Kim Lee Sim, Stephen L Hoffman, Peter G Kremsner
A highly protective malaria vaccine would greatly facilitate the prevention and elimination of malaria and containment of drug-resistant parasites. A high level (more than 90%) of protection against malaria in humans has previously been achieved only by immunization with radiation-attenuated Plasmodium falciparum (Pf) sporozoites (PfSPZ) inoculated by mosquitoes; by intravenous injection of aseptic, purified, radiation-attenuated, cryopreserved PfSPZ ('PfSPZ Vaccine'); or by infectious PfSPZ inoculated by mosquitoes to volunteers taking chloroquine or mefloquine (chemoprophylaxis with sporozoites)...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28196536/community-engagement-and-the-social-context-of-targeted-malaria-treatment-a-qualitative-study-in-kayin-karen-state-myanmar
#12
Kate Sahan, Christopher Pell, Frank Smithuis, Aung Kyaw Phyo, Sai Maung Maung, Chanida Indrasuta, Arjen M Dondorp, Nicholas J White, Nicholas P J Day, Lorenz von Seidlein, Phaik Yeong Cheah
BACKGROUND: The spread of artemisinin-resistance in Plasmodium falciparum is a threat to current global malaria control initiatives. Targeted malaria treatment (TMT), which combines mass anti-malarial administration with conventional malaria prevention and control measures, has been proposed as a strategy to tackle this problem. The effectiveness of TMT depends on high levels of population coverage and is influenced by accompanying community engagement activities and the local social context...
February 14, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28195463/target-elucidation-by-cocrystal-structures-of-nadh-ubiquinone-oxidoreductase-of-plasmodium-falciparum-pfndh2-with-small-molecule-to-eliminate-drug-resistant-malaria
#13
Yiqing Yang, You Yu, Xiaolu Li, Jing Li, Yue Wu, Jie Yu, Jingpeng Ge, Zhenghui Huang, Lubin Jiang, Yu Rao, Maojun Yang
Drug-resistant malarial strains have been continuously emerging recently, which posts a great challenge for the global health. Therefore, new antimalarial drugs with novel targeting mechanisms are urgently needed for fighting drug-resistant malaria. NADH-ubiquinone oxidoreductase of Plasmodium falciparum (PfNDH2) represents a viable target for antimalarial drug development. However, the absence of structural information on PfNDH2 limited rational drug design and further development. Herein, we report high resolution crystal structures of the PfNDH2 protein for the first time in Apo-, NADH-, and RYL-552 (a new inhibitor)-bound states...
February 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28193656/within-host-selection-of-drug-resistance-in-a-mouse-model-reveals-dose-dependent-selection-of-atovaquone-resistance-mutations
#14
Suci Nuralitha, Lydia S Murdiyarso, Josephine E Siregar, Din Syafruddin, Jessica Roelands, Jan Verhoef, Andy I M Hoepelman, Sangkot Marzuki
The evolutionary selection of malaria parasites within individual host plays a critical role in the emergence of drug resistance. We have compared the selection of atovaquone resistance mutant in mouse models reflecting two different causes of failure in malaria treatment, inadequate sub-therapeutic dose and incomplete therapeutic dose.The two models are based on cycles of insufficient treatment of P. berghei-infected mice: repeated inadequate treatment associated with sub-therapeutic dose (0.1 mg Kg(-1) BW; RIaT) and repeated incomplete treatment with therapeutic dose (14...
February 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28193646/simplified-reversed-chloroquines-to-overcome-malaria-resistance-to-quinoline-based-drugs
#15
Bornface Gunsaru, Steven J Burgess, Westin Morrill, Jane X Kelly, Shawheen Shomloo, Martin J Smilkstein, Katherine Liebmann, David H Peyton
Building on our earlier work of attaching a chemosensitizer (reversal agent) to a known drug pharmacophore, we have now expanded the structure-activity relationship study to include simplified versions of the chemosensitizer. The change from two aromatic rings in this head group to a single ring, in fact, does not appear to detrimentally affect the antimalarial activity of the compounds. Data from in vitro heme binding and β-hematin inhibition assays suggest that the single aromatic RCQ compounds retain similar activities against P...
February 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28192434/adverse-effects-of-mefloquine-for-the-treatment-of-uncomplicated-malaria-in-thailand-a-pooled-analysis-of-19-850-individual-patients
#16
Sue J Lee, Feiko O Ter Kuile, Ric N Price, Christine Luxemburger, François Nosten
Mefloquine (MQ) has been used for the treatment of malaria since the mid-1980s, first as monotherapy or as fixed combination with sulfadoxine-pyrimethamine (MSP) and since the mid-1990s in combination with artesunate. There is a renewed interested in MQ as part of a triple therapy for the treatment of multi-drug resistance P. falciparum malaria. The widespread use of MQ beyond south-East Asia has been constrained by reports of poor tolerability. Here we present the side effect profile of MQ for the treatment of uncomplicated malaria on the Thai-Myanmar/Cambodia borders...
2017: PloS One
https://www.readbyqxmd.com/read/28187990/how-to-contain-artemisinin-and-multidrug-resistant-falciparum-malaria
#17
REVIEW
Arjen M Dondorp, Frank M Smithuis, Charley Woodrow, Lorenz von Seidlein
In the Greater Mekong subregion (GMS), artemisinin resistance is increasingly compounded by partner drug resistance, causing high failure rates of artemisinin combination therapies in some areas. For its containment, an accelerated elimination strategy will be needed. This includes high-quality implementation of conventional malaria control measures: early case management with quality artemisinin combination therapies (avoiding artesunate monotherapies) and single gametocytocidal low dose of primaquine, vector control and surveillance...
February 7, 2017: Trends in Parasitology
https://www.readbyqxmd.com/read/28179098/genome-wide-association-studies-of-drug-resistance-determinants
#18
REVIEW
Sarah K Volkman, Jonathan Herman, Amanda K Lukens, Daniel L Hartl
Population genetic strategies that leverage association, selection, and linkage have identified drug-resistant loci. However, challenges and limitations persist in identifying drug-resistance loci in malaria. In this review we discuss the genetic basis of drug resistance and the use of genome-wide association studies, complemented by selection and linkage studies, to identify and understand mechanisms of drug resistance and response. We also discuss the implications of nongenetic mechanisms of drug resistance recently reported in the literature, and present models of the interplay between nongenetic and genetic processes that contribute to the emergence of drug resistance...
October 27, 2016: Trends in Parasitology
https://www.readbyqxmd.com/read/28178358/substrate-analogous-inhibitors-exert-antimalarial-action-by-targeting-the-plasmodium-lactate-transporter-pffnt-at-nanomolar-scale
#19
André Golldack, Björn Henke, Bärbel Bergmann, Marie Wiechert, Holger Erler, Alexandra Blancke Soares, Tobias Spielmann, Eric Beitz
Resistance against all available antimalarial drugs calls for novel compounds that hit unexploited targets in the parasite. Here, we show that the recently discovered Plasmodium falciparum lactate/proton symporter, PfFNT, is a valid druggable target, and describe a new class of fluoroalkyl vinylogous acids that potently block PfFNT and kill cultured parasites. The original compound, MMV007839, is derived from the malaria box collection of potent antimalarials with unknown targets and contains a unique internal prodrug principle that reversibly switches between a lipophilic transport form and a polar, substrate-analogous active form...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28174312/selective-whole-genome-amplification-is-a-robust-method-that-enables-scalable-whole-genome-sequencing-of-plasmodium-vivax-from-unprocessed-clinical-samples
#20
Annie N Cowell, Dorothy E Loy, Sesh A Sundararaman, Hugo Valdivia, Kathleen Fisch, Andres G Lescano, G Christian Baldeviano, Salomon Durand, Vince Gerbasi, Colin J Sutherland, Debbie Nolder, Joseph M Vinetz, Beatrice H Hahn, Elizabeth A Winzeler
: Whole-genome sequencing (WGS) of microbial pathogens from clinical samples is a highly sensitive tool used to gain a deeper understanding of the biology, epidemiology, and drug resistance mechanisms of many infections. However, WGS of organisms which exhibit low densities in their hosts is challenging due to high levels of host genomic DNA (gDNA), which leads to very low coverage of the microbial genome. WGS of Plasmodium vivax, the most widely distributed form of malaria, is especially difficult because of low parasite densities and the lack of an ex vivo culture system...
February 7, 2017: MBio
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