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K13 propeller

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
Lucie Paloque, Benoit Witkowski, Joël Lelièvre, Manel Ouji, Tanila Ben Haddou, Frédéric Ariey, Anne Robert, Jean-Michel Augereau, Didier Ménard, Bernard Meunier, Françoise Benoit-Vical
Background: Owing to the emergence of multiresistant Plasmodium falciparum parasites in Southeast Asia, along with the impressive decrease in the efficacy of the endoperoxide compound artemisinin and of artemisinin-based combination therapies, the development of novel antimalarial drugs or combinations is required. Although several antiplasmodial molecules, such as endoperoxide-based compounds, are in advanced research or development, we do not know whether resistance to artemisinin derivatives might impact the efficacy of these new compounds...
February 1, 2018: Journal of Antimicrobial Chemotherapy
Papichaya Phompradit, Wanna Chaijaroenkul, Kesara Na-Bangchang
The recent reports of high failure rates and decline in in vitro sensitivity of Plasmodium falciparum to artemisinin-based combination therapies (ACTs) suggest the possibility of clinical artemisinin resistance along the Thai-Cambodian and Thai-Myanmar borders. The study investigated cellular mechanisms of action and resistance of P. falciparum to artesunate (stage specific activity, interaction with hemozoin, and anti-oxidant levels) in the two paired P. falciparum isolates (MSF046 and MSF060) collected before treatment with a 3-day artesunate-mefloquine and at the time of recrudescence...
December 2017: Parasitology Research
Warangkhana Songsungthong, Supasak Kulawonganunchai, Alisa Wilantho, Sissades Tongsima, Pongpisid Koonyosying, Chairat Uthaipibull, Sumalee Kamchonwongpaisan, Philip J Shaw
BACKGROUND: The current first line drugs for treating uncomplicated malaria are artemisinin (ART) combination therapies. However, Plasmodium falciparum parasites resistant to ART and partner drugs are spreading, which threatens malaria control efforts. Rodent malaria species are useful models for understanding antimalarial resistance, in particular genetic variants responsible for cross resistance to different compounds. METHODS: The Plasmodium berghei RC strain (PbRC) is described as resistant to different antimalarials, including chloroquine (CQ) and ART...
2017: PeerJ
Madeline Montenegro, Aaron T Neal, Maritza Posada, Briegel De Las Salas, Tatiana M Lopera-Mesa, Rick M Fairhurst, Alberto Tobon-Castaño
High treatment failure rates for Plasmodium falciparum malaria have been reported in Colombia for chloroquine, amodiaquine, and sulfadoxine-pyrimethamine. Artemisinin combination therapies were introduced in 2006 in Colombia, where artemether-lumefantrine (AL) is currently used to treat uncomplicated P. falciparum malaria. Artemisinin (ART) resistance was initially observed in Southeast Asia as an increased parasite clearance time, manifesting as a positive thick-blood smear on day 3 after treatment (D3 positivity)...
December 2017: Antimicrobial Agents and Chemotherapy
Soy Ty Kheang, Siv Sovannaroth, Sovann Ek, Say Chy, Phally Chhun, Sokkieng Mao, Sokomar Nguon, Dy Soley Lek, Didier Menard, Neeraj Kak
BACKGROUND: The presence of artemisinin-resistant malaria parasites was confirmed in western Cambodia in 2009. In 2013, mutations in the propeller domain of the kelch protein K13 was found to be associated with artemisinin resistance. A cross-sectional study was conducted to determine the prevalence of Day-3 parasitaemia, estimate the frequency of k13 molecular marker and assess their relationship in the context of operational research. METHODS: Blood smears and filter paper blood spots were collected from febrile patients in Kravanh District, Pursat Province...
September 13, 2017: Malaria Journal
Mohammad Shafiul Alam, Benedikt Ley, Maisha Khair Nima, Fatema Tuj Johora, Mohammad Enayet Hossain, Kamala Thriemer, Sarah Auburn, Jutta Marfurt, Ric N Price, Wasif A Khan
BACKGROUND: Artemisinin resistance is present in the Greater Mekong region and poses a significant threat for current anti-malarial treatment guidelines in Bangladesh. The aim of this molecular study was to assess the current status of drug resistance in the Chittagong Hill Tracts of Bangladesh near the Myanmar border. METHODS: Samples were obtained from patients enrolled into a Clinical Trial (NCT02389374) conducted in Alikadam, Bandarban between August 2014 and January 2015...
August 15, 2017: Malaria Journal
Myat Htut Nyunt, Myat Thu Soe, Hla Win Myint, Htet Wai Oo, Moe Moe Aye, Soe Soe Han, Ni Ni Zaw, Cho Cho, Phyo Zaw Aung, Khin Thiri Kyaw, Thin Thin Aye, Naychi Aung San, Leonard Ortega, Krongthong Thimasarn, Maria Dorina G Bustos, Sherwin Galit, Mohammad Rafiul Hoque, Pascal Ringwald, Eun-Taek Han, Myat Phone Kyaw
BACKGROUND: Emergence of artemisinin-resistant malaria in Southeast Asian countries threatens the global control of malaria. Although K13 kelch propeller has been assessed for artemisinin resistance molecular marker, most of the mutations need to be validated. In this study, artemisinin resistance was assessed by clinical and molecular analysis, including k13 and recently reported markers, pfarps10, pffd and pfmdr2. METHODS: A prospective cohort study in 1160 uncomplicated falciparum patients was conducted after treatment with artemisinin-based combination therapy (ACT), in 6 sentinel sites in Myanmar from 2009 to 2013...
August 14, 2017: Malaria Journal
Chengyun Yang, Hongwei Zhang, Ruimin Zhou, Dan Qian, Ying Liu, Yuling Zhao, Suhua Li, Bianli Xu
BACKGROUND: Henan Province has been in the malaria elimination stage, with all reports of the disease being imported since 2012 and over 90% coming from Africa. Surveillance and population studies are essential for the early detection and subsequent prevention of the spread of drug resistance. The K13-propeller gene was recently identified as a proposed molecular marker of artemisinin (ART) resistance. In this study, we detected mutations of the K13-propeller gene in samples taken from imported malaria cases in Henan Province from 2012 to 2015...
August 10, 2017: BMC Infectious Diseases
Joseph Allico Djaman, Dagnogo Olefongo, Aristide Berenger Ako, Jocelyne Roman, Vincent Foumane Ngane, Leonardo K Basco, Rachida Tahar
Artemisinin-resistant malaria has not been reported from Africa, but resistance can possibly spread from Asia or arise independently in Africa. The emergence of artemisinin resistance in Africa can be monitored by molecular assay of Kelch 13 (K13) propeller sequences. A total of 251 archived DNA samples of Plasmodium falciparum isolates collected in 2002, 2003, and 2006 in Yaounde, Cameroon, and 47 samples collected in 2006 and 2013 in Abidjan, Côte d'Ivoire, were analyzed for K13-propeller sequence polymorphism...
July 2017: American Journal of Tropical Medicine and Hygiene
Sweta Mishra, Praveen K Bharti, Man M Shukla, Nazia A Ali, Sher S Kashyotia, Avdhesh Kumar, Akshay C Dhariwal, Neeru Singh
The spread of P. falciparum resistant strain has led to a significant resurgence of malaria morbidity and mortality. The current cornerstone in malaria treatment in India is Artemisinin based Combination (Artesunate + Sulphadoxine-Pyrimethamine) Therapy (ACT) for treatment of uncomplicated P. falciparum malaria since 2010. In the present study we assessed the therapeutic efficacy of ACT and molecular monitoring of antimalarial resistance. Therapeutic efficacy was determined by in vivo method using 28 days follow-up...
June 2017: Pathogens and Global Health
Marylin Madamet, Mame Bou Kounta, Khalifa Ababacar Wade, Gora Lo, Silman Diawara, Mansour Fall, Raymond Bercion, Aminata Nakoulima, Khadidiatou Ba Fall, Nicolas Benoit, Mamadou Wague Gueye, Bécaye Fall, Bakary Diatta, Bruno Pradines
In 2006, the Senegalese National Malaria Control Programme recommended artemisinin-based combination therapy as first-line treatment for uncomplicated malaria. In addition, intravenous (i.v.) injection of artesunate and artemether has gradually replaced quinine for the treatment of severe malaria. Mutations in the propeller domain of the Kelch 13 gene (K13-propeller, PF3D71343700), such as Y493H, R539T, I543T and C580Y, were recently associated with in vivo and in vitro resistance to artemisinin in Southeast Asia...
June 2017: International Journal of Antimicrobial Agents
Moe Kyaw Myint, Charlotte Rasmussen, Aung Thi, Dorina Bustos, Pascal Ringwald, Khin Lin
BACKGROUND: In Myanmar, three types of artemisinin-based combination therapy (ACT) are recommended as first-line treatment of uncomplicated falciparum malaria: artemether-lumefantrine (AL), artesunate-mefloquine (AS + MQ), and dihydroartemisinin-piperaquine (DP). Resistance to both artemisinins and ACT partner drugs has been reported from the Greater Mekong Sub-region, and regular efficacy monitoring of the recommended ACT is conducted in Myanmar. This paper reports on results from studies to monitor the efficacy of the three forms of ACT in sentinel sites in northern Myanmar, and investigations of mutations in the Kelch13 (k13) propeller domain...
April 7, 2017: Malaria Journal
Hong-Wei Zhang, San-Jin Li, Tao Hu, Yong-Min Yu, Cheng-Yun Yang, Rui-Min Zhou, Ying Liu, Jing Tang, Jing-Jing Wang, Xiu-Yun Wang, Yong-Xiang Sun, Zhan-Chun Feng, Bian-Li Xu
BACKGROUND: The spleen plays a pivotal role in the rapid clearance of parasitized red blood cells in patients with falciparum malaria after artemisinin treatment. Prolonged parasite clearance can be found in patients who have had a splenectomy, or those with hemoglobin abnormalities and/or reduced immunity, which are all distinguishable from artemisinin resistance. This paper reports on a case of prolonged parasite clearance in a Chinese splenectomized patient with falciparum malaria imported from Nigeria...
April 4, 2017: Infectious Diseases of Poverty
Didier Menard, Arjen Dondorp
Increasing antimalarial drug resistance once again threatens effective antimalarial drug treatment, malaria control, and elimination. Artemisinin combination therapies (ACTs) are first-line treatment for uncomplicated falciparum malaria in all endemic countries, yet partial resistance to artemisinins has emerged in the Greater Mekong Subregion. Concomitant emergence of partner drug resistance is now causing high ACT treatment failure rates in several areas. Genetic markers for artemisinin resistance and several of the partner drugs have been established, greatly facilitating surveillance...
March 13, 2017: Cold Spring Harbor Perspectives in Medicine
Souleymane Dama, Hamidou Niangaly, Amed Ouattara, Issaka Sagara, Sekou Sissoko, Oumar Bila Traore, Amadou Bamadio, Niawanlou Dara, Moussa Djimde, Mohamed Lamine Alhousseini, Siaka Goita, Hamma Maiga, Antoine Dara, Ogobara K Doumbo, Abdoulaye A Djimde
BACKGROUND: Artemisinin-based combination therapy is the recommended first-line treatment for uncomplicated falciparum malaria worldwide. However, recent studies conducted in Mali showed an increased frequency of recurrent parasitaemia following artemether-lumefantrine (AL) treatment. METHODS: Study samples were collected during a large WANECAM study. Ex-vivo Plasmodium falciparum sensitivity to artemether and lumefantrine was assessed using the tritiated hypoxanthine-based assay...
February 2, 2017: Malaria Journal
Nguyen Thuy-Nhien, Nguyen Kim Tuyen, Nguyen Thanh Tong, Nguyen Tuong Vy, Ngo Viet Thanh, Huynh Thuy Van, Pham Huong-Thu, Huynh Hong Quang, Maciej F Boni, Christiane Dolecek, Jeremy Farrar, Guy E Thwaites, Olivo Miotto, Nicholas J White, Tran Tinh Hien
The spread of artemisinin-resistant Plasmodium falciparum compromises the therapeutic efficacy of artemisinin combination therapies (ACTs) and is considered the greatest threat to current global initiatives to control and eliminate malaria. This is particularly relevant in Vietnam, where dihydroartemisinin-piperaquine (DP) is the recommended ACT for P. falciparum infection. The propeller domain gene of K13, a molecular marker of artemisinin resistance, was successfully sequenced in 1,060 P. falciparum isolates collected at 3 malaria hot spots in Vietnam between 2009 and 2016...
April 2017: Antimicrobial Agents and Chemotherapy
Fabian Baumgärtner, Joëlle Jourdan, Christian Scheurer, Benjamin Blasco, Brice Campo, Pascal Mäser, Sergio Wittlin
BACKGROUND: Recently published data suggest that artemisinin derivatives and synthetic peroxides, such as the ozonides OZ277 and OZ439, have a similar mode of action. Here the cross-resistance of OZ277 and OZ439 and four additional next-generation ozonides was probed against the artemisinin-resistant clinical isolate Plasmodium falciparum Cam3.I, which carries the K13-propeller mutation R539T (Cam3.I(R539T)). METHODS: The previously described in vitro ring-stage survival assay (RSA0-3h) was employed and a simplified variation of the original protocol was developed...
January 25, 2017: Malaria Journal
Eldin Talundzic, Yaye D Ndiaye, Awa B Deme, Christian Olsen, Dhruviben S Patel, Shweta Biliya, Rachel Daniels, Fredrik O Vannberg, Sarah K Volkman, Venkatachalam Udhayakumar, Daouda Ndiaye
The emergence of Plasmodium falciparum resistance to artemisinin in Southeast Asia threatens malaria control and elimination activities worldwide. Multiple polymorphisms in the P. falciparum kelch gene found in chromosome 13 (Pfk13) have been associated with artemisinin resistance. Surveillance of potential drug resistance loci within a population that may emerge under increasing drug pressure is an important public health activity. In this context, P. falciparum infections from an observational surveillance study in Senegal were genotyped using targeted amplicon deep sequencing (TADS) for Pfk13 polymorphisms...
March 2017: Antimicrobial Agents and Chemotherapy
Betty Balikagala, Toshihiro Mita, Mie Ikeda, Miki Sakurai, Shouki Yatsushiro, Nobuyuki Takahashi, Shin-Ichiro Tachibana, Mary Auma, Edward H Ntege, Daisuke Ito, Eizo Takashima, Nirianne Marie Q Palacpac, Thomas G Egwang, Joseph Okello Onen, Masatoshi Kataoka, Eisaku Kimura, Toshihiro Horii, Takafumi Tsuboi
BACKGROUND: Individual drug treatment may select resistant parasites in the human body, a process termed in vivo selection. Some single nucleotide polymorphisms in Plasmodium falciparum chloroquine-resistance transporter (pfcrt) and multidrug resistance gene 1 (pfmdr1) genes have been reportedly selected after artemether-lumefantrine treatment. However, there is a paucity of data regarding in vivo selection of P. falciparum Kelch propeller domain (pfkelch13) polymorphisms, responsible for artemisinin-resistance in Asia, and six putative background mutations for artemisinin resistance; D193Y in ferredoxin, T484I in multiple resistance protein 2, V127M in apicoplast ribosomal protein S10, I356T in pfcrt, V1157L in protein phosphatase and C1484F in phosphoinositide-binding protein...
January 9, 2017: Malaria Journal
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