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https://www.readbyqxmd.com/read/28214367/population-genetic-structure-and-adaptation-of-malaria-parasites-on-the-edge-of-endemic-distribution
#1
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
#2
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
#3
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/28212636/experimental-hut-evaluation-of-a-novel-long-lasting-non-pyrethroid-durable-wall-lining-for-control-of-pyrethroid-resistant-anopheles-gambiae-and-anopheles-funestus-in-tanzania
#4
Robert Malima, Basiliana Emidi, Louisa A Messenger, Richard M Oxborough, Bernard Batengana, Wema Sudi, Sophie Weston, George Mtove, Joseph P Mugasa, Franklin W Mosha, Mark W Rowland, William Kisinza
BACKGROUND: A novel, insecticide-treated, durable wall lining (ITWL), which mimics indoor residual spraying (IRS), has been developed to provide prolonged vector control when fixed to the inner walls of houses. PermaNet(®) ITWL is a polypropylene material containing non-pyrethroids (abamectin and fenpyroximate) which migrate gradually to the surface. METHODS: An experimental hut trial was conducted in an area of pyrethroid-resistant Anopheles gambiae s.l. and Anopheles funestus s...
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
#5
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/28206868/mosquito-vector-biology-and-control-in-latin-america-a-26th-symposium
#6
Lee W Cohnstaedt, Catalina Alfonso-Para, Ildefonso Fernandez-Salas
The 26th Annual Latin American Symposium presented by the American Mosquito Control Association (AMCA) was held as part of the 82nd Annual Meeting of the AMCA in Savannah, GA, in February 2016. The principal objective, as for the previous 25 symposia, was to promote participation in the AMCA by vector control specialists, public health workers, and academicians from Latin America. This publication includes summaries of 19 presentations that were given orally in Spanish by participants from Colombia, Ecuador, Mexico, and the USA...
December 2016: Journal of the American Mosquito Control Association
https://www.readbyqxmd.com/read/28199305/sterile-protection-against-human-malaria-by-chemoattenuated-pfspz-vaccine
#7
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
#8
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-co-crystal-structures-of-nadh-ubiquinone-oxidoreductase-of-plasmodium-falciparum-pfndh2-with-small-molecule-to-eliminate-drug-resistant-malaria
#9
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 anti-malarial 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 anti-malarial drug development. However, the absence of structural information of 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 14, 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
#10
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/28193647/piperaquine-population-pharmacokinetics-and-cardiac-safety-in-cambodia
#11
Pattaraporn Vanachayangkul, Chanthap Lon, Michele Spring, Sommethy Sok, Winita Ta-Aksorn, Chanikarn Kodchakorn, Sut-Thang Pann, Soklyda Chann, Mali Ittiverakul, Sabaithip Sriwichai, Nillawan Buathong, Worachet Kuntawunginn, Mary So, Theng Youdaline, Erin Milner, Mariusz Wojnarski, Charlotte Lanteri, Jessica Manning, Satharath Prom, Mark Haigney, Louis Cantilena, David Saunders
Despite rising resistance, dihydroartemisinin-piperaquine (DP) remains a first line therapy for uncomplicated malaria in many parts of Cambodia. While generally well-tolerated as a 3-day regimen, compressed 2-day regimens were associated with treatment-limiting cardiac repolarization effects in a recent clinical trial. To better estimate the risks of piperaquine concentration on QT interval prolongation, we pooled data from 3 randomized clinical trials between 2010 and 2014 in northern Cambodia. A population pharmacokinetic model was developed to compare exposure-response relationships between 2-day (2DP) and 3-day (3DP) regimens while accounting for differences in regimen and sample collection times between studies...
February 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28193646/simplified-reversed-chloroquines-to-overcome-malaria-resistance-to-quinoline-based-drugs
#12
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/28193292/the-effect-of-elevated-temperatures-on-the-life-history-and-insecticide-resistance-phenotype-of-the-major-malaria-vector-anopheles-arabiensis-diptera-culicidae
#13
Shüné V Oliver, Basil D Brooke
BACKGROUND: Temperature plays a crucial role in the life history of insects. Recent climate change research has highlighted the importance of elevated temperature on malaria vector distribution. This study aims to examine the role of elevated temperatures on epidemiologically important life-history traits in the major malaria vector, Anopheles arabiensis. Specifically, the differential effects of temperature on insecticide-resistant and susceptible strains were examined. METHODS: Two laboratory strains of A...
February 14, 2017: Malaria Journal
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
#14
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/28191507/mapping-the-distribution-of-anopheles-funestus-across-benin-highlights-a-sharp-contrast-of-susceptibility-to-insecticides-and-infection-rate-to-plasmodium-between-southern-and-northern-populations
#15
Rousseau Djouaka, Romaric Akoton, Genevieve M Tchigossou, Seun M Atoyebi, Helen Irving, Michael O Kusimo, Innocent Djegbe, Jacob M Riveron, Eric Tossou, Akadiri Yessoufou, Charles S Wondji
Background. Malaria remains an important public health issue in Benin, with Anopheles gambiae s.l. and Anopheles funestus s.s being the predominant vectors. This study was designed to generate information on An. funestus distribution, molecular speciation, Plasmodium infection rate and insecticide susceptibility status across Benin. Methods. Mosquito samples were collected from December 2014 to January 2016 in 46 localities in Benin. These samples were mapped and An. funestus collected were speciated to the molecular level...
December 14, 2016: Wellcome Open Res
https://www.readbyqxmd.com/read/28187990/how-to-contain-artemisinin-and-multidrug-resistant-falciparum-malaria
#16
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/28183236/antimalarial-antiplasmodial-and-analgesic-activities-of-root-extract-of-alchornea-laxiflora
#17
Jude E Okokon, Nkemnele Bensella Augustine, Dinesh Mohanakrishnan
CONTEXT: Alchornea laxiflora (Benth.) Pax. & Hoffman (Euphorbiaceae) root decoctions are traditionally used in the treatment of malaria and pain in Nigeria. OBJECTIVE: To assess the antimalarial, antiplasmodial and analgesic potentials of root extract and fractions against malarial infections and chemically-induced pains. MATERIAL AND METHODS: The root extract and fractions of Alchornea laxiflora were investigated for antimalarial activity against Plasmodium berghei infection in mice, antiplasmodial activity against chloroquine sensitive (Pf 3D7) and resistant (Pf INDO) strains of Plasmodium falciparum using SYBR green assay method and analgesic activity against experimentally-induced pain models...
December 2017: Pharmaceutical Biology
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/28178359/the-malaria-parasite-s-lactate-transporter-pffnt-is-the-target-of-antiplasmodial-compounds-identified-in-whole-cell-phenotypic-screens
#19
Sanduni V Hapuarachchi, Simon A Cobbold, Sarah H Shafik, Adelaide S M Dennis, Malcolm J McConville, Rowena E Martin, Kiaran Kirk, Adele M Lehane
In this study the 'Malaria Box' chemical library comprising 400 compounds with antiplasmodial activity was screened for compounds that perturb the internal pH of the malaria parasite, Plasmodium falciparum. Fifteen compounds induced an acidification of the parasite cytosol. Two of these did so by inhibiting the parasite's formate nitrite transporter (PfFNT), which mediates the H+-coupled efflux from the parasite of lactate generated by glycolysis. Both compounds were shown to inhibit lactate transport across the parasite plasma membrane, and the transport of lactate by PfFNT expressed in Xenopus laevis oocytes...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28178358/substrate-analogous-inhibitors-exert-antimalarial-action-by-targeting-the-plasmodium-lactate-transporter-pffnt-at-nanomolar-scale
#20
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
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