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Artemisinin resistance

Frances Rocamora, Lei Zhu, Kek Yee Liong, Arjen Dondorp, Olivo Miotto, Sachel Mok, Zbynek Bozdech
Due to their remarkable parasitocidal activity, artemisinins represent the key components of first-line therapies against Plasmodium falciparum malaria. However, the decline in efficacy of artemisinin-based drugs jeopardizes global efforts to control and ultimately eradicate the disease. To better understand the resistance phenotype, artemisinin-resistant parasite lines were derived from two clones of the 3D7 strain of P. falciparum using a selection regimen that mimics how parasites interact with the drug within patients...
March 14, 2018: PLoS Pathogens
Janie Anne Zuber, Shannon Takala-Harrison
Based on the emergence and spread throughout the Greater Mekong Subregion (GMS) of multiple artemisinin-resistant lineages, the prevalence of multidrug resistance leading to high rates of artemisinin-based combination treatment failure in parts of the GMS, and the declining malaria burden in the region, the World Health Organization has recommended complete elimination of falciparum malaria from the GMS. Mass drug administration (MDA) is being piloted as one elimination intervention to be employed as part of this effort...
2018: Infection and Drug Resistance
Ishag Adam, Yassin Ibrahim, Gasim I Gasim
BACKGROUND: Malaria is a major public health problem in endemic countries including Sudan, where about 75% of populations are at risk. Due to widespread of chloroquine-resistant strains of Plasmodium falciparum, artemisinin-based combination therapy (ACT) is currently treatment of choice for malaria in the vast majority of malaria-endemic countries. This systematic review and meta-analysis is performed to obtain an overall stronger evidence of the outcomes of ACT in the treatment of uncomplicated falciparum malaria from the existing literature in Sudan...
March 13, 2018: Malaria Journal
Laurent Dembele, Devendra Kumar Gupta, Michelle Yi-Xiu Lim, Xiaoman Ang, Jeremy J Selva, Kesinee Chotivanich, Chea Nguon, Arjen M Dondorp, Ghislain M C Bonamy, Thierry T Diagana, Pablo Bifani
Artemisinin (ART) resistance has spread through Southeast Asia, posing serious threat to the control and elimination of malaria. ART resistance has been associated with mutations in the Plasmodium falciparum kelch-13 ( Pfk13 ) propeller domain. Phenotypically, ART resistance is defined as delayed parasite clearance in patients' due to the reduced susceptibility of early ring-stage parasites to the active metabolite of ART dihydroartemisinin (DHA). Early rings can enter a state of quiescence upon DHA exposure and resume growth in its absence...
March 12, 2018: Antimicrobial Agents and Chemotherapy
Lin Lin, Xuefang Mao, Yanhui Sun, Haiying Cui
A new inhibitor to overcome the multi-drug resistance of MRSA was developed in this study. Artemisinin (ART) was encapsulated in beta-cyclodextrin (β-CD) in order to enhance the solubility of ART. The molecular encapsulation of ART was confirmed by using Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), X-Ray Diffraction (XRD), and nuclear magnetic resonance (1 H NMR) methods. The phase solubility study showed the relationship between ART solubility and β-CD concentration. The antibacterial activity of ART/β-CDs inclusion complexes (ART/β-CDs-IC) (20 mg/mL) against MRSA was distinguished, with the inhibition rate of 99...
March 9, 2018: Microbial Pathogenesis
P Nkoli Mandoko, V Sinou, D Moke Mbongi, D Ngoyi Mumba, G Kahunu Mesia, J Losimba Likwela, S Bi Shamamba Karhemere, L Muepu Tshilolo, J-J Tamfum Muyembe, D Parzy
OBJECTIVE: Artemisinin-based combination therapies have been available since 2005 in the Democratic Republic of the Congo to treat malaria and to overcome the challenge of anti-malarial drug resistance as well as to improve access to effective treatments. The private sector is the primary distribution source for anti-malarial drugs and thus, has a key position among the supply chain actors for a rational and proper use of anti-malarial drugs. We aimed to assess access to nationally recommended anti-malarial drugs in private sector pharmacies of the capital-city of Kinshasa...
March 9, 2018: Médecine et Maladies Infectieuses
Tryphena Adams, Nana Aba A Ennuson, Neils B Quashie, Godfred Futagbi, Sena Matrevi, Oheneba C K Hagan, Benjamin Abuaku, Kwadwo A Koram, Nancy O Duah
BACKGROUND: Plasmodium falciparum delayed clearance with the use of artemisinin-based combination therapy (ACTs) has been reported in some African countries. Single nucleotide polymorphisms (SNPs) in two genes, P. falciparum adaptor protein complex 2 mu subunit (pfap2mu) and ubiquitin specific protease 1 (pfubp1), have been linked to delayed clearance with ACT use in Kenya and recurrent imported malaria in Britain. With over 12 years of ACT use in Ghana, this study investigated the prevalence of SNPs in the pfap2mu and pfubp1 in Ghanaian clinical P...
March 12, 2018: Parasites & Vectors
Mathieu Gendrot, Francis Tsombeng Foguim, Marie Gladys Robert, Rémy Amalvict, Joel Mosnier, Nicolas Benoit, Marylin Madamet, Bruno Pradines
BACKGROUND: Plasmodium falciparum resistance to artemisinin-based combination therapy has emerged and spread in Southeast Asia. In areas where artemisinin resistance is emerging, the efficacy of combination is now based on partner drugs. In this context, the identification of novel markers of resistance is essential to monitor the emergence and spread of resistance to these partner drugs. The ubiquitylation pathway could be a possible target for anti-malarial compounds and might be involved in resistance...
March 12, 2018: Malaria Journal
Pooja Agarwal, A R Anvikar, C R Pillai, Kumkum Srivastava
Background & objectives: : The in vitro assays for susceptibility of Plasmodium falciparum to antimalarial drugs are important tools for monitoring drug resistance. During the present study, efforts were made to establish long-term continuous in vitro culture of Indian field isolates of P. falciparum and to determine their sensitivity to standard antimalarial drugs and antibiotics. Methods: Four (MZR-I, -II, -III and -IV) P. falciparum isolates were obtained from four patients who showed artemisinin-based combination therapy (ACT) from Mizoram, a north-eastern State of India, and characterized for their in vitro susceptibility to chloroquine diphosphate (CQ), quinine hydrochloride dehydrate, mefloquine, piperaquine, artemether, arteether, dihydro-artemisinin (DHA), lumefantrine and atovaquone and antibiotics, azithromycin and doxycycline...
November 2017: Indian Journal of Medical Research
Kunitaka Yoshida, Mitsuhiro Iyori, Andrew M Blagborough, Ahmed M Salman, Pawan Dulal, Katarzyna A Sala, Daisuke S Yamamoto, Shahid M Khan, Chris J Janse, Sumi Biswas, Tatsuya Yoshii, Yenni Yusuf, Masaharu Tokoro, Adrian V S Hill, Shigeto Yoshida
With the increasing prevalence of artemisinin-resistant malaria parasites, a highly efficacious and durable vaccine for malaria is urgently required. We have developed an experimental virus-vectored vaccine platform based on an envelope-modified baculovirus dual-expression system (emBDES). Here, we show a conceptually new vaccine platform based on an adenovirus-prime/emBDES-boost heterologous immunization regimen expressing the Plasmodium falciparum circumsporozoite protein (PfCSP). A human adenovirus 5-prime/emBDES-boost heterologous immunization regimen consistently achieved higher sterile protection against transgenic P...
March 1, 2018: Scientific Reports
David Langlais, Regina Cencic, Neda Moradin, James M Kennedy, Kodjo Ayi, Lauren E Brown, Ian Crandall, Michael J Tarry, Martin Schmeing, Kevin C Kain, John A Porco, Jerry Pelletier, Philippe Gros
Cerebral malaria (CM) is a severe and rapidly progressing complication of infection by Plasmodium parasites that is associated with high rates of mortality and morbidity. Treatment options are currently few, and intervention with artemisinin (Art) has limited efficacy, a problem that is compounded by the emergence of resistance to Art in Plasmodium parasites. Rocaglates are a class of natural products derived from plants of the Aglaia genus that have been shown to interfere with eukaryotic initiation factor 4A (eIF4A), ultimately blocking initiation of protein synthesis...
March 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
Huguette Gaelle Ngassa Mbenda, Weilin Zeng, Yao Bai, Faiza Amber Siddiqui, Zhaoqing Yang, Liwang Cui
Artemisinin resistance in Plasmodium falciparum was associated with mutations in the propeller domain of the PfK13 gene and increased phosphotidylinositol-3-phosphate kinase (PfPI3K) activity. Assessment of the genetic diversity of the orthologue of PfK13 gene i.e. PvK12 in Plasmodium vivax field samples from the same hotspots of P. falciparum artemisinin resistance revealed a limited genetic diversity of PvK12. Following the same logic, we analyzed genetic variations of the PvPI3K gene in 188 P. vivax field isolates from two geographic locations along the China-Myanmar border...
February 17, 2018: Infection, Genetics and Evolution
Dragan Ljolje, Pedro Rafael Dimbu, Julia Kelley, Ira Goldman, Douglas Nace, Aleixo Macaia, Eric S Halsey, Pascal Ringwald, Filomeno Fortes, Venkatachalam Udhayakumar, Eldin Talundzic, Naomi W Lucchi, Mateusz M Plucinski
BACKGROUND: Artemisinin-based combination therapy is the first-line anti-malarial treatment for uncomplicated Plasmodium falciparum infection in Angola. To date, the prevalence of polymorphisms in the pfk13 gene, associated with artemisinin resistance, and pfmdr1, associated with lumefantrine resistance, have not been systematically studied in Angola. METHODS: DNA was isolated from pretreatment and late treatment failure dried blood spots collected during the 2015 round of therapeutic efficacy studies in Benguela, Lunda Sul, and Zaire Provinces in Angola...
February 20, 2018: Malaria Journal
Muhammad Ismail, Longbing Ling, Yawei Du, Chen Yao, Xinsong Li
Artemisinin and its derivatives are highly effective drugs in the treatment of P. falciparum malaria. However, their clinical applications face challenges because of short half-life, poor bioavailability and growing drug resistance. In this article, novel dimeric artesunate phospholipid (Di-ART-GPC) based liposomes were developed by combination of dimerization and self-assembly to address these shortcomings. Firstly, Di-ART-GPC conjugate was synthesized by a facile esterification of artesunate (ART) and glycerophosphorylcholine (GPC) and confirmed by MS,1 H NMR and13 C NMR...
May 2018: Biomaterials
Shilpy Aggarwal, Deepika Paliwal, Dhirender Kaushik, Girish Kumar Gupta, Ajay Kumar
BACKGROUND: Malaria, one of the most vital infectious diseases caused by protozoan parasites of the Plasmodium genus. As P. falciparum, the cause of most of the severe cases of malaria, is increasingly resistant to available drugs such as amodioquine, chloroquine, artemisinin, and antifolates, there is an urgent need of identify new targets for chemotherapy Objective: This study screened novel pyrazole derivatives carrying iminium & benzothiazole group for antimalarial potential against P...
February 12, 2018: Combinatorial Chemistry & High Throughput Screening
A Raffetin, F Bruneel, C Roussel, M Thellier, P Buffet, E Caumes, S Jauréguiberry
INTRODUCTION: Artesunate and other artemisinin derivatives are used in various infectious and non-infectious diseases. We aimed to analyze available data on artesunate and artemisinin derivatives activity in humans and their potential clinical benefits in non-malarial indications. MATERIAL AND METHODS: Literature review performed on PubMed and the Cochrane Library databases using the PRISMA method. We analyzed studies published in English from January 2008 to August 2017 using the same indicators of drug efficacy...
February 5, 2018: Médecine et Maladies Infectieuses
Supriya Sharma, Ram Suresh Bharti, Nitin Bhardwaj, Anupkumar R Anvikar, Neena Valecha, Neelima Mishra
BACKGROUND: Antimalarial drug resistance is a potential threat for control and elimination of malaria. To ascertain the status of antimalarial drug resistance at the study sites, correlation between in vitro drug sensitivity pattern and drug resistance molecular markers in Plasmodium falciparum malaria was undertaken. MATERIALS AND METHODS: Polymorphisms in P. falciparum chloroquine resistance transporter (pfcrt) K76T and pfmdr1 N86Y were studied in relation to the in vitro susceptibility of P...
October 2017: Indian Journal of Medical Microbiology
Mahamane Haidara, Mohamed Haddad, Adama Denou, Guillaume Marti, Sandra Bourgeade-Delmas, Rokia Sanogo, Geneviève Bourdy, Agnès Aubouy
BACKGROUND: Plasmodium falciparum malaria is still one of the most deadly pathology worldwide. Efficient treatment is jeopardized by parasite resistance to artemisinin and its derivatives, and by poor access to treatment in endemic regions. Anti-malarial traditional remedies still offer new tracks for identifying promising antiplasmodial molecules, and a way to ensure that all people have access to care. The present study aims to validate the traditional use of Terminalia macroptera, a Malian plant used in traditional medicine...
February 5, 2018: Malaria Journal
Roberto Amato, Richard D Pearson, Jacob Almagro-Garcia, Chanaki Amaratunga, Pharath Lim, Seila Suon, Sokunthea Sreng, Eleanor Drury, Jim Stalker, Olivo Miotto, Rick M Fairhurst, Dominic P Kwiatkowski
BACKGROUND: Antimalarial resistance is rapidly spreading across parts of southeast Asia where dihydroartemisinin-piperaquine is used as first-line treatment for Plasmodium falciparum malaria. The first published reports about resistance to antimalarial drugs came from western Cambodia in 2013. Here, we analyse genetic changes in the P falciparum population of western Cambodia in the 6 years before those reports. METHODS: We analysed genome sequence data on 1492 P falciparum samples from 11 locations across southeast Asia, including 464 samples collected in western Cambodia between 2007 and 2013...
February 1, 2018: Lancet Infectious Diseases
Christiane Prosser, Wieland Meyer, John Ellis, Rogan Lee
Molecular surveillance of antimalarial drug resistance markers has become an important part of resistance detection and containment. In the current climate of multidrug resistance, including resistance to the global front-line drug artemisinin, there is a consensus to upscale molecular surveillance. The most salient limitation to current surveillance efforts is that skill and infrastructure requirements preclude many regions. This includes sub-Saharan Africa, where Plasmodium falciparum is responsible for most of the global malaria disease burden...
January 23, 2018: Trends in Parasitology
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