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Artemisinin resistance

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https://www.readbyqxmd.com/read/28935919/split-dosing-of-artemisinins-does-not-improve-antimalarial-therapeutic-efficacy
#1
N J White, J Watson, E A Ashley
It has been suggested recently, based on pharmacokinetic-pharmacodynamic modelling exercises, that twice daily dosing of artemisinins increases malaria parasite killing and so could "dramatically enhance and restore drug effectiveness" in artemisinin resistant P. falciparum malaria infections. It was recommended that split dosing should be incorporated into all artemisinin combination regimen designs. To explain why parasite clearance rates were not faster with split dose regimens it was concluded that splenic malaria parasite clearance capacity was readily exceeded, resulting in the accumulation of dead parasites in the circulation, that parasite clearance was therefore an unreliable measure of drug efficacy, and instead that human immunity is the primary determinant of clearance rates...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28934435/declining-transmission-and-immunity-to-malaria-and-emerging-artemisinin-resistance-in-thailand-a-longitudinal-study
#2
Ricardo Ataíde, Rosanna Powell, Kerryn Moore, Alistair McLean, Aung Pyae Phyo, Shalini Nair, Marina White, Tim J Anderson, James G Beeson, Julie A Simpson, Francois Nosten, Freya J I Fowkes
Background: Reductions in malaria transmission decrease naturally acquired immunity, which may influence the emergence of Plasmodium falciparum artemisinin-resistant phenotypes and genotypes over time. Methods: Antibodies specific for P. falciparum antigens were determined in uncomplicated hyperparasitemic malaria patients over a 10-year period of declining malaria transmission and emerging artemisinin resistance in northwestern Thailand. We investigated the association between antibody levels and both parasite clearance time (PCt½) and artemisinin resistance-associated kelch13 genotypes over time...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28927405/the-use-of-respondent-driven-sampling-to-assess-malaria-knowledge-treatment-seeking-behaviours-and-preventive-practices-among-mobile-and-migrant-populations-in-a-setting-of-artemisinin-resistance-in-western-cambodia
#3
Po Ly, Julie Thwing, Colleen McGinn, Cesia E Quintero, Narann Top-Samphor, Najibullah Habib, Jack S Richards, Sara E Canavati, Seshu Babu Vinjamuri, Chea Nguon
BACKGROUND: Multi-drug-resistant Plasmodium falciparum threatens malaria elimination efforts in Cambodia and the Greater Mekong Subregion (GMS). Malaria burden in the GMS is higher among certain high-risk demographic groups in Cambodia, especially among migrant and mobile populations (MMPs). This respondent driven sampling (RDS) study was conducted in order to determine malaria knowledge, treatment-seeking behaviours and preventive practices among two MMP groups in Western Cambodia. METHODS: An RDS survey of MMPs was implemented in four purposively-selected communes along the Thai-Cambodia border; two in Veal Veang District and two in Pailin Province, chosen due to their sizeable MMP groups, their convenience of access, and their proximity to Thailand, which allowed for comparison with RDS studies in Thailand...
September 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28923866/changing-antimalarial-drug-sensitivities-in-uganda
#4
Stephanie A Rasmussen, Frida G Ceja, Melissa D Conrad, Patrick K Tumwebaze, Oswald Byaruhanga, Thomas Katairo, Samuel L Nsobya, Philip J Rosenthal, Roland A Cooper
Dihydroartemisinin-piperaquine (DP) has demonstrated excellent efficacy for the treatment and prevention of malaria in Uganda. However, resistance to both components of this regimen has emerged in Southeast Asia. The efficacy of artemether-lumefantrine, the first-line regimen to treat malaria in Uganda, has also been excellent, but continued pressure may select for parasites with decreased sensitivity to lumefantrine. To gain insight into current drug sensitivity patterns, ex vivo sensitivities were assessed and genotypes previously associated with altered drug sensitivity were characterized for 58 isolates collected in Tororo, Uganda from subjects presenting in 2016 with malaria from the community or as part of a clinical trial comparing DP chemoprevention regimens...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28903759/knowledge-access-and-utilization-of-bed-nets-among-stable-and-seasonal-migrants-in-an-artemisinin-resistance-containment-area-of-myanmar
#5
Wint Phyo Than, Tin Oo, Khin Thet Wai, Aung Thi, Philip Owiti, Binay Kumar, Hemant Deepak Shewade, Rony Zachariah
BACKGROUND: Myanmar lies in the Greater Mekong sub-region of South-East Asia faced with the challenge of emerging resistance to artemisinin combination therapies (ACT). Migrant populations are more likely than others to spread ACT resistance. A vital intervention to reduce malaria transmission, resistance spread and eliminate malaria is the use of bed nets. Among seasonal and stable migrants in an artemisinin resistance containment region of Myanmar, we compared a) their household characteristics, b) contact with health workers and information material, and c) household knowledge, access and utilization of bed nets...
September 14, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28903755/prevalence-of-k13-mutation-and-day-3-positive-parasitaemia-in-artemisinin-resistant-malaria-endemic-area-of-cambodia-a-cross-sectional-study
#6
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
https://www.readbyqxmd.com/read/28895080/population-pharmacokinetic-and-pharmacodynamic-modeling-of-artemisinin-resistance-in-southeast-asia
#7
Jesmin Lohy Das, Arjen M Dondorp, Francois Nosten, Aung Pyae Phyo, Warunee Hanpithakpong, Pascal Ringwald, Pharath Lim, Nicholas J White, Mats O Karlsson, Martin Bergstrand, Joel Tarning
Orally administered artemisinin-based combination therapy is the first-line treatment against uncomplicated P. falciparum malaria worldwide. However, the increasing prevalence of artemisinin resistance is threatening efforts to treat and eliminate malaria in Southeast Asia. This study aimed to characterize the exposure-response relationship of artesunate in patients with artemisinin sensitive and resistant malaria infections. Patients were recruited in Pailin, Cambodia (n = 39), and Wang Pha, Thailand (n = 40), and received either 2 mg/kg/day of artesunate mono-therapy for 7 consecutive days or 4 mg/kg/day of artesunate monotherapy for 3 consecutive days followed by mefloquine 15 and 10 mg/kg for 2 consecutive days...
September 11, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28893264/maximizing-research-study-effectiveness-in-malaria-elimination-settings-a-mixed-methods-study-to-capture-the-experiences-of-field-based-staff
#8
Sara E Canavati, Cesia E Quintero, Britt Haller, Dysoley Lek, Sovann Yok, Jack S Richards, Maxine Anne Whittaker
BACKGROUND: In a drug-resistant, malaria elimination setting like Western Cambodia, field research is essential for the development of novel anti-malarial regimens and the public health solutions necessary to monitor the spread of resistance and eliminate infection. Such field studies often face a variety of similar implementation challenges, but these are rarely captured in a systematic way or used to optimize future study designs that might overcome similar challenges. Field-based research staff often have extensive experience and can provide valuable insight regarding these issues, but their perspectives and experiences are rarely documented and seldom integrated into future research protocols...
September 11, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28886522/quantification-of-the-antimalarial-drug-pyronaridine-in-whole-blood-using-lc-ms-ms-increased-sensitivity-resulting-from-reduced-non-specific-binding
#9
Daniel Blessborn, Karnrawee Kaewkhao, Lijiang Song, Nicholas J White, Nicholas P J Day, Joel Tarning
Malaria is one of the most important parasitic diseases of man. The development of drug resistance in malaria parasites is an inevitable consequence of their widespread and often unregulated use. There is an urgent need for new and effective drugs. Pyronaridine is a known antimalarial drug that has received renewed interest as a partner drug in artemisinin-based combination therapy. To study its pharmacokinetic properties, particularly in field settings, it is necessary to develop and validate a robust, highly sensitive and accurate bioanalytical method for drug measurements in biological samples...
August 26, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28875841/new-molecular-targets-and-strategies-for-antimalarial-discovery
#10
Anna Caroline Aguiar, Lorena R F de Sousa, Celia R S Garcia, Glaucius Oliva, Rafael V C Guido
Malaria remains a major health problem, especially because of the emergence of resistant P. falciparum strains to artemisinin derivatives. In this context, safe and affordable antimalarial drugs are desperately needed. New proteins have been investigated as molecular targets for research and development of innovative compounds with well-defined mechanism of action. In this review, we highlight genetically and clinically validated plasmodial proteins as drug targets for the next generation of therapeutics. The enzymes described herein are involved in hemoglobin hydrolysis, the invasion process, elongation factors for protein synthesis, pyrimidine biosynthesis, post-translational modifications such as prenylation, phosphorylation and histone acetylation, generation of ATP in mitochondrial metabolism and aminoacylation of RNAs...
August 29, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28864166/artemisinin-permeability-via-caco-2-cells-increases-after-simulated-digestion-of-artemisia-annua-leaves
#11
Matthew R Desrosiers, Pamela J Weathers
ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia annua has been used for > 2000yrs to treat fever and is more recently known for producing the important antimalarial drug, artemisinin. AIM OF THE STUDY: Artemisinin combination therapies (ACTs) are effective for treating malaria, but are often unavailable to those in need. Dried leaves of A. annua (DLA) have recently been studied as a cost effective alternative to traditional ACTs. DLA was shown to dramatically increase oral bioavailability compared to pure artemisinin, so more investigation into the mechanisms causing this increased bioavailability is needed...
August 31, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28860870/early-treatment-failure-in-concurrent-dengue-and-mixed-malaria-species-infection-with-suspected-resistance-to-artemisinin-combination-therapy-from-a-tertiary-care-center-in-delhi-a-case-report
#12
Rushika Saksena, Monika Matlani, Vineeta Singh, Amit Kumar, Anupam Anveshi, Dilip Kumar, Rajni Gaind
BACKGROUND: Concurrent dengue and mixed malaria infections in a single patient present with overlapping clinical manifestations which pose a diagnostic challenge and management dilemma in areas of common endemicities. METHODS: We report a case of a young male who tested positive for both Plasmodium vivax and Plasmodium falciparum along with dengue infection. He showed signs of early treatment failure to artemisinin combination therapy (artesunate with sulfadoxine+pyrimethamine)...
2017: International Medical Case Reports Journal
https://www.readbyqxmd.com/read/28856028/bibliometric-analysis-of-worldwide-publications-on-antimalarial-drug-resistance-2006-2015
#13
REVIEW
Waleed M Sweileh, Samah W Al-Jabi, Ansam F Sawalha, Adham S AbuTaha, Sa'ed H Zyoud
BACKGROUND: In response to international efforts to control and eradicate malaria, we designed this study to give a bibliometric overview of research productivity in antimalarial drug resistance (AMDR). METHODS: Keywords related to AMDR were used to retrieve relevant literature using Scopus database. RESULTS: A total of 976 publications with an h-index of 63 were retrieved. The number of publications showed a noticeable increase starting in the early 1990s...
2017: Malaria Research and Treatment
https://www.readbyqxmd.com/read/28854635/partner-drug-resistance-and-population-substructuring-of-artemisinin-resistant-plasmodium-falciparum-in-cambodia
#14
Christian M Parobek, Jonathan B Parr, Nicholas F Brazeau, Chanthap Lon, Suwanna Chaorattanakawee, Panita Gosi, Eric J Barnett, Lauren D Norris, Steven R Meshnick, Michele D Spring, Charlotte A Lanteri, Jeffrey A Bailey, David L Saunders, Jessica T Lin, Jonathan J Juliano
Plasmodium falciparum in western Cambodia has developed resistance to artemisinin and its partner drugs, causing frequent treatment failure. Understanding this evolution can inform the deployment of new therapies. We investigated the genetic architecture of 78 falciparum isolates using whole-genome sequencing, correlating results to in vivo and ex vivo drug resistance and exploring the relationship between population structure, demographic history, and partner drug resistance. Principle component analysis, network analysis and demographic inference identified a diverse central population with three clusters of clonally expanding parasite populations, each associated with specific K13 artemisinin resistance alleles and partner drug resistance profiles which were consistent with the sequential deployment of artemisinin combination therapies in the region...
June 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28831224/phenotypic-approach-artemisinin-resistance-in-malaria-rodent-as-in-vivo-model
#15
Lilik Maslachah, Thomas V Widiyatno, Lita Rakhma Yustinasari, Hani Plumeriastuti
AIM: The aim of this study is to prove the development of artemisinin resistance phenotypically in malaria rodent as an in vivo resistance development model in humans. MATERIALS AND METHODS: Plasmodium berghei was infected intraperitoneally in mice, then artemisinin was given with "4-day-test" with effective dose (ED) 99% dose for 3 days which begins 48 h after infection (D2, D3, and D4). Parasite development was followed during 5(th) until 10(th) days of infection...
July 2017: Veterinary World
https://www.readbyqxmd.com/read/28807879/apigenin-induced-abcc1-mediated-efflux-of-glutathione-from-mature-erythrocytes-inhibits-the-proliferation-of-plasmodium-falciparum
#16
Ohud Fallatah, Elias Georges
Plasmodium falciparum infection of mature normal erythrocytes leads to heightened oxidative stress that is tolerated in normal but not in erythrocytes from sickle-cell, β-thalassemia, and glucose-6-phosphate dehydrogenase (G6PD) deficiency hosts. In this report, it was of interest to perturb the redox homeostasis of normal erythrocytes through drug-induced active efflux of glutathione via erythrocyte ABCC1 (member of the C- subfamily of the human ATP-binding cassette (ABC) transporters). To achieve this objective, we made use of apigenin, shown previously to activate ABCC1 glutathione efflux in mature erythrocytes...
August 11, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28806961/molecular-analysis-demonstrates-high-prevalence-of-chloroquine-resistance-but-no-evidence-of-artemisinin-resistance-in-plasmodium-falciparum-in-the-chittagong-hill-tracts-of-bangladesh
#17
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
https://www.readbyqxmd.com/read/28806957/clinical-and-molecular-surveillance-of-artemisinin-resistant-falciparum-malaria-in-myanmar-2009-2013
#18
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
https://www.readbyqxmd.com/read/28806082/the-discovery-of-novel-antimalarial-aminoxadiazoles-as-a-promising-nonendoperoxide-scaffold
#19
Elena Sandoval, María José Lafuente-Monasterio, María J Almela, Pablo Castañeda, María Belén Jiménez Díaz, María S Martínez-Martínez, Jaume Vidal, Íñigo Angulo-Barturen, Paul Bamborough, Jeremy Burrows, Nicholas Cammack, María J Chaparro, José M Coterón, Cristina de Cozar, Benigno Crespo, Beatriz Díaz, Gerard Drewes, Esther Fernández, Santiago Ferrer-Bazaga, María Teresa Fraile, Francisco J Gamo, Sonja Ghidelli-Disse, Rubén Gómez, John Haselden, Sophie Huss, María Luisa León, Jaime de Mercado, Simon J F Macdonald, José Ignacio Martín Hernando, Sara Prats, Margarita Puente, Anne Rodríguez, Juan C de la Rosa, Lourdes Rueda, Carolyn Selenski, Paul Willis, David M Wilson, Michael Witty, Félix Calderón
Since the appearance of resistance to the current front-line antimalarial treatments, ACTs (artemisinin combination therapies), the discovery of novel chemical entities to treat the disease is recognized as a major global health priority. From the GSK antimalarial set, we identified an aminoxadiazole with an antiparasitic profile comparable with artemisinin (1), with no cross-resistance in a resistant strains panel and a potential new mode of action. A medicinal chemistry program allowed delivery of compounds such as 19 with high solubility in aqueous media, an acceptable toxicological profile, and oral efficacy...
August 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28797235/polymorphisms-of-plasmodium-falciparum-k13-propeller-gene-among-migrant-workers-returning-to-henan-province-china-from-africa
#20
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
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