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Malaria drug resistance

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https://www.readbyqxmd.com/read/29229871/antifolate-drug-resistance-novel-mutations-and-haplotype-distribution-in-dhps-and-dhfr-from-northeast-india
#1
N P Sarmah, K Sarma, D R Bhattacharyya, A A Sultan, D Bansal, N Singh, P K Bharti, R Sehgal, P K Mohapatra, P Parida, J Mahanta
Malaria is a major public health concern in Northeast India with a preponderance of drug-resistant strains. Until recently the partner drug for artemisinin combination therapy (ACT) was sulphadoxine pyrimethamine (SP). Antifolate drug resistance has been associated with the mutations at dihydropteroate synthase (dhps) and dihydrofolatereductase (dhfr) genes. This study investigated antifolate drug resistance at the molecular level. A total of 249 fever cases from Arunachal Pradesh, NE India, were screened for malaria, and of these, 75 were found to be positive for Plasmodium falciparum...
December 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/29227011/synthesis-of-novel-benzimidazole-acrylonitriles-for-inhibition-of-plasmodium-falciparum-growth-by-dual-target-inhibition
#2
Kalicharan Sharma, Apeksha Shrivastava, Ram N Mehra, Girdhar S Deora, Mohammad M Alam, Mohammad S Zaman, Mymoona Akhter
Antimalarial drug resistance has emerged as a threat for treating malaria, generating a need to design and develop newer, more efficient antimalarial agents. This research aimed to identify novel leads as antimalarials. Dual receptor mechanism could be a good strategy to combat developing drug resistance. A series of benzimidazole acrylonitriles containing 18 compounds were designed, synthesized and evaluated for cytotoxicity, heme binding, ferriprotoporphyrin IX biomineralisation inhibition, and falcipain-2 enzyme assay...
December 11, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/29220419/high-resolution-single-cell-sequencing-of-malaria-parasites
#3
Simon G Trevino, Standwell C Nkhoma, Shalini Nair, Benjamin J Daniel, Karla Moncada, Stanley Khoswe, Rachel L Banda, François Nosten, Ian H Cheeseman
Single-cell genomics is a powerful tool for determining the genetic architecture of complex communities of unicellular organisms. In areas of high transmission, malaria patients are often challenged by the activities of multiple Plasmodium falciparum lineages, which can potentiate pathology, spread drug resistance loci and also complicate most genetic analysis. Single-cell sequencing of P. falciparum would be key to understanding infection complexity, though efforts are hampered by the extreme nucleotide composition of its genome (∼80% AT-rich)...
December 6, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29219249/activities-of-11-azaartemisinin-and-n-sulfonyl-derivatives-against-asexual-and-transmissible-malaria-parasites
#4
Rozanne Harmse, Dina Coertzen, Ho Ning Wong, Frans J Smit, Mariette E van der Watt, Janette Reader, Sindiswe H Nondaba, Lyn-Marie Birkholtz, Richard K Haynes, David D N'Da
Dihydroartemisinin (DHA), either used in its own right or as the active drug generated in vivo from the other artemisinins in current clinical use-artemether and artesunate-induces quiescence in ring-stage parasites of Plasmodium falciparum (Pf). This induction of quiescence is linked to artemisinin resistance. Thus, we have turned to structurally disparate artemisinins that are incapable of providing DHA on metabolism. Accordingly, 11-azaartemisinin 5 and selected N-sulfonyl derivatives were screened against intraerythrocytic asexual stages of drug-sensitive Pf NF54 and drug-resistant K1 and W2 parasites...
December 8, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29215279/design-and-synthesis-of-orally-bioavailable-piperazine-substituted-4-1h-quinolones-with-potent-antimalarial-activity-structure-activity-and-structure-property-relationship-studies
#5
Raghupathi Neelarapu, Jordany R Maignan, Cynthia L Lichorowic, Andrii Monastyrskyi, Tina S Mutka, Alexis N LaCrue, Lynn D Blake, Debora Casandra, Sherwin Mashkouri, Jeremy N Burrows, Paul A Willis, Dennis E Kyle, Roman Manetsch
Malaria deaths have been decreasing over the last 10-15 years, with global mortality rates having fallen by 47% since 2000. While the World Health Organization (WHO) recommends the use of artemisinin-based combination therapies (ACTs) to combat malaria, the emergence of artemisinin resistant strains underscores the need to develop new antimalarial drugs. Recent in vivo efficacy improvements of the historical antimalarial ICI 56,780 have been reported, however with the poor solubility and rapid development of resistance, this compound requires further optimization...
December 7, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29213208/awareness-of-malaria-and-treatment-seeking-behaviour-among-persons-with-acute-undifferentiated-fever-in-the-endemic-regions-of-myanmar
#6
Phyo Aung Naing, Thae Maung Maung, Jaya Prasad Tripathy, Tin Oo, Khin Thet Wai, Aung Thi
Background: Myanmar has a high burden of malaria with two-third of the population at risk of malaria. One of the basic elements of the Roll Back Malaria Initiative to fight against malaria is early diagnosis and treatment within 24 h of fever. Public awareness about malaria is a key factor in malaria prevention and control and in improving treatment-seeking behaviour. Methods: A large community-based survey was carried out in 27 townships of malaria endemic regions in Myanmar in 2015 which reported on the knowledge, behaviour and practices around malaria in the general population...
2017: Tropical Medicine and Health
https://www.readbyqxmd.com/read/29193799/preliminary-evaluation-of-artemisinin-cholesterol-conjugates-as-potential-drugs-for-treatment-of-intractable-forms-of-malaria-and-tuberculosis
#7
Mokhitli Morake, Dina Coertzen, Andile Ngwane, Johannes Wentzel, Ho Ning Wong, Frans Smit, Lyn-Marie Birkholtz, Ray-Dean Petersen, Bienyameen Baker, Ian Wiid, David N'Da, Richard K Haynes
In order to evaluate the feasibility of developing drugs that may be active against both malaria and tuberculosis (TB) by utilizing in part putative cholesterol transporters in the causative pathogens and through enhancement of passive diffusion in granulomatous TB, artemisinin-cholesterol conjugates were synthesized by connecting the component molecules through various linkers. The compounds were screened in vitro against Plasmodium falciparum (Pf) and Mycobacterium tuberculosis (Mtb). Antimalarial activities (IC50) against Pf drug sensitive NF54, and drug resistant K1 and W2 strains ranged from 0...
November 28, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29192183/prevalence-of-mutations-linked-to-antimalarial-resistance-in-plasmodium-falciparum-from-chhattisgarh-central-india-a-malaria-elimination-point-of-view
#8
Priyanka Patel, Praveen K Bharti, Devendra Bansal, Nazia A Ali, Rajive K Raman, Pradyumna K Mohapatra, Rakesh Sehgal, Jagadish Mahanta, Ali A Sultan, Neeru Singh
Antimalarial drug resistance is a major global challenge in malaria control and elimination. Mutations in six different genes of Plasmodium falciparum (crt, mdr1, dhfr, dhps, ATPase6 and K-13 propeller) that confer resistance to chloroquine, sulphadoxine-pyrimethamine and artemisinin-based combination therapy were analyzed in samples from Chhattisgarh. Seventy-eight percent of the samples were found to have a pfcrt mutation (53% double, 24% triple and 1% single mutant), and 59% of pfmdr1 genes were found to have an N86Y mutation...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29190671/malera-an-updated-research-agenda-for-insecticide-and-drug-resistance-in-malaria-elimination-and-eradication
#9
REVIEW
(no author information available yet)
Resistance to first-line treatments for Plasmodium falciparum malaria and the insecticides used for Anopheles vector control are threatening malaria elimination efforts. Suboptimal responses to drugs and insecticides are both spreading geographically and emerging independently and are being seen at increasing intensities. Whilst resistance is unavoidable, its effects can be mitigated through resistance management practices, such as exposing the parasite or vector to more than one selective agent. Resistance contributed to the failure of the 20th century Global Malaria Eradication Programme, and yet the global response to this issue continues to be slow and poorly coordinated-too often, too little, too late...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29190295/malera-an-updated-research-agenda-for-combination-interventions-and-modelling-in-malaria-elimination-and-eradication
#10
(no author information available yet)
This paper summarises key advances and priorities since the 2011 presentation of the Malaria Eradication Research Agenda (malERA), with a focus on the combinations of intervention tools and strategies for elimination and their evaluation using modelling approaches. With an increasing number of countries embarking on malaria elimination programmes, national and local decisions to select combinations of tools and deployment strategies directed at malaria elimination must address rapidly changing transmission patterns across diverse geographic areas...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29190291/malera-an-updated-research-agenda-for-diagnostics-drugs-vaccines-and-vector-control-in-malaria-elimination-and-eradication
#11
(no author information available yet)
Since the turn of the century, a remarkable expansion has been achieved in the range and effectiveness of products and strategies available to prevent, treat, and control malaria, including advances in diagnostics, drugs, vaccines, and vector control. These advances have once again put malaria elimination on the agenda. However, it is clear that even with the means available today, malaria control and elimination pose a formidable challenge in many settings. Thus, currently available resources must be used more effectively, and new products and approaches likely to achieve these goals must be developed...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29183370/towards-malaria-elimination-in-savannakhet-lao-pdr-mathematical-modelling-driven-strategy-design
#12
Sai Thein Than Tun, Lorenz von Seidlein, Tiengkham Pongvongsa, Mayfong Mayxay, Sompob Saralamba, Shwe Sin Kyaw, Phetsavanh Chanthavilay, Olivier Celhay, Tran Dang Nguyen, Thu Nguyen-Anh Tran, Daniel M Parker, Maciej F Boni, Arjen M Dondorp, Lisa J White
BACKGROUND: The number of Plasmodium falciparum malaria cases around the world has decreased substantially over the last 15 years, but with the spread of resistance against anti-malarial drugs and insecticides, this decline may not continue. There is an urgent need to consider alternative, accelerated strategies to eliminate malaria in countries like Lao PDR, where there are a few remaining endemic areas. A deterministic compartmental modelling tool was used to develop an integrated strategy for P...
November 28, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29178921/plasmodium-falciparum-kelch-13-mutations-and-treatment-response-in-patients-in-hpa-pun-district-northern-kayin-state-myanmar
#13
Craig A Bonnington, Aung Pyae Phyo, Elizabeth A Ashley, Mallika Imwong, Kanlaya Sriprawat, Daniel M Parker, Stephane Proux, Nicholas J White, Francois Nosten
BACKGROUND: Artemisinin resistance, linked to polymorphisms in the Kelch gene on chromosome 13 of Plasmodium falciparum (k13), has outpaced containment efforts in South East Asia. For national malaria control programmes in the region, it is important to establish a surveillance system which includes monitoring for k13 polymorphisms associated with the clinical phenotype. METHODS: Between February and December 2013, parasite clearance was assessed in 35 patients with uncomplicated P...
November 25, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29174651/cancer-combination-therapy-of-the-sesquiterpenoid-artesunate-and-the-selective-egfr-tyrosine-kinase-inhibitor-erlotinib
#14
Thomas Efferth
BACKGROUND: The shift from cytotoxic to targeted chemotherapy led to improved treatment outcomes in oncology. Nevertheless, many cancer patients cannot be cured from their disease because of the development of drug resistance and side effects. PURPOSE: There is an ongoing quest for novel compounds, which raised not only the interest in natural products but also in novel combination therapy regimens. STUDY DESIGN: In this review, we report on the inhibition epidermal growth factor receptor (EGFR) by targeted small molecules and their combination with natural products from medicinal plants...
November 10, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29162636/quantitative-proteomic-profiling-reveals-novel-plasmodium-falciparum-surface-antigens-and-possible-vaccine-candidates
#15
Sandra K Nilsson Bark, Rushdy Ahmad, Kathleen Dantzler, Amanda K Lukens, Mariana De Niz, Matthew J Szucs, Xiaojing Jin, Joanne Cotton, Dietmar Hoffmann, Eva Bric-Furlong, Ray Oomen, Mark Parrington, Dan Milner, Daniel E Neafsey, Steven A Carr, Dyann F Wirth, Matthias Marti
Despite recent efforts towards control and elimination, malaria remains a major public health problem worldwide. Plasmodium falciparum resistance against artemisinin, used in front line combination drugs, is on the rise, and the only approved vaccine shows limited efficacy. Combinations of novel and tailored drug and vaccine interventions are required to maintain the momentum of the current malaria elimination program. Current evidence suggests that strain-transcendent protection against malaria infection can be achieved using whole organism vaccination or with a polyvalent vaccine covering multiple antigens or epitopes...
November 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29161011/the-design-of-plasmodium-vivax-hypoxanthine-guanine-phosphoribosyltransferase-inhibitors-as-potential-antimalarial-therapeutics
#16
Dianne T Keough, Dominik Rejman, Radek Pohl, Eva Zborníková, Dana Hockova, Tristan Croll, Michael D Edstein, Geoff W Birrell, Marina Chavchich, Lieve M J Naesens, Gregory K Pierens, Ian M Brereton, Luke W Guddat
Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) are the foremost causative agents of malaria. Due to the development of resistance to current antimalarial medications, new drugs for this parasitic disease need to be discovered. The activity of hypoxanthine-guanine-[xanthine]-phosphoribosyltransferase, HG[X]PRT, is reported to be essential for the growth of both of these parasites, making it an excellent target for antimalarial drug discovery. Here, we have used rational structure-based methods to design an inhibitor, [3R,4R]-4-guanin-9-yl-3-((S)-2-hydroxy-2-phosphonoethyl)oxy-1-N-(phosphonopropionyl)pyrrolidine, of PvHGPRT and PfHGXPRT which has Ki values of 8 nM and 7 nM, respectively for these two enzymes...
November 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29160791/antimalarial-activity-of-acetylenic-thiophenes-from-echinops-hoehnelii-schweinf
#17
Helen Bitew, Wendimagegn Mammo, Ariaya Hymete, Mariamawit Yonathan Yeshak
Malaria is one of the world's most severe endemic diseases and due to the emergence of resistance to the currently available medicines, the need for new targets and relevant antimalarial drugs remains acute. The crude extract, four solvent fractions and two isolated compounds from the roots of Echinops hoehnelii were tested for their antimalarial activity using the standard four-day suppressive method in Plasmodium berghei-infected mice. The 80% methanol extract exhibited suppression of 4.6%, 27.8%, 68.5% and 78...
November 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29158278/characterization-of-plasmodium-atg3-atg8-interaction-inhibitors-identifies-novel-alternative-mechanisms-of-action-in-toxoplasma-gondii
#18
Joseph M Varberg, Kaice A LaFavers, Gustavo Arrizabalaga, William J Sullivan
Protozoan parasites, including the apicomplexan pathogens Plasmodium falciparum (malaria) and Toxoplasma gondii (toxoplasmosis) infect millions of people world-wide and represent a major human disease burden. Despite their prevalence, therapeutic strategies to treat these infections remain limited and are threatened by the emergence of drug resistance, highlighting the need for the identification of novel drug targets. Recently, homologues of the core autophagy proteins, including Atg8 and Atg3, were identified in many protozoan parasites...
November 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29155671/capacity-development-through-the-us-president-s-malaria-initiative-supported-antimalarial-resistance-monitoring-in-africa-network
#19
Eric S Halsey, Meera Venkatesan, Mateusz M Plucinski, Eldin Talundzic, Naomi W Lucchi, Zhiyong Zhou, Celine I Mandara, Hawela Moonga, Busiku Hamainza, Abdoul Habib Beavogui, Simon Kariuki, Aaron M Samuels, Laura C Steinhardt, Don P Mathanga, Julie Gutman, Yves Eric Denon, Aline Uwimana, Ashenafi Assefa, Jimee Hwang, Ya Ping Shi, Pedro Rafael Dimbu, Ousmane Koita, Deus S Ishengoma, Daouda Ndiaye, Venkatachalam Udhayakumar
Antimalarial drug resistance is an evolving global health security threat to malaria control. Early detection of Plasmodium falciparum resistance through therapeutic efficacy studies and associated genetic analyses may facilitate timely implementation of intervention strategies. The US President's Malaria Initiative-supported Antimalarial Resistance Monitoring in Africa Network has assisted numerous laboratories in partner countries in acquiring the knowledge and capability to independently monitor for molecular markers of antimalarial drug resistance...
December 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29155091/dynamic-molecular-events-associated-to-plasmodium-berghei-gametogenesis-through-proteomic-approach
#20
Carlos H S Garcia, Delphine Depoix, Rayner M L Queiroz, Jaques M F Souza, Wagner Fontes, Marcelo V de Sousa, Marlon D M Santos, Paulo C Carvalho, Philippe Grellier, Sébastien Charneau
Plasmodium mature sexual cycle occurs in the vector mosquitoes and ensures the transmission to a new host. Gametogenesis takes place within minutes in the vector midgut. Gametocytes have to complete a deep nuclear reorganization, quick differentiation, and in the case of male gametocytes, intracytoplasmic flagellum assembly that results in free-swimming microgametes required for macrogamete fertilization. In efforts to improve our knowledge of molecular mechanisms involved in gamete morphogenesis, we carried out a nanoLC/MSMS based quantitative proteomic analysis throughout the xanthurenic acid-induced gametogenesis of the rodent parasite P...
November 15, 2017: Journal of Proteomics
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