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Artemisinin resistance

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https://www.readbyqxmd.com/read/28438929/molecular-profile-of-malaria-drug-resistance-markers-of-plasmodium-falciparum-in-suriname
#1
Stella M Chenet, Sheila Akinyi Okoth, Julia Kelley, Naomi Lucchi, Curtis S Huber, Stephen Vreden, Alexandre Macedo de Oliveira, John W Barnwell, Venkatachalam Udhayakumar, Malti R Adhin
In Suriname, an artesunate monotherapy therapeutic efficacy trial was recently conducted to evaluate partial artemisinin resistance emerging in Plasmodium falciparum We genotyped the PfK13 propeller domain of P. falciparum in forty samples as well as other mutations proposed to be associated with artemisinin resistant mutants. We did not find any mutations previously associated with artemisinin resistance in Southeast Asia but we found fixed resistance mutations for chloroquine and sulfadoxine-pyrimethamine...
April 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28438194/malaria-profiles-and-challenges-in-artemisinin-resistance-containment-in-myanmar
#2
Thet Wai Nwe, Tin Oo, Khin Thet Wai, Shuisen Zhou, Johan van Griensven, Palanivel Chinnakali, Safieh Shah, Aung Thi
BACKGROUND: This study examined evolving malaria profiles from January, 2010 to December, 2014 to evaluate achievements and challenges of implementing measures to prevent and control spread of artemisinin resistance in Myanmar. METHODS: Using National Malaria Control Programme (NMCP) data, a cross-sectional descriptive study of 52 townships in artemisinin-resistant containment areas in Myanmar was conducted. Annual program data were analysed, and trends over time are graphically presented...
April 25, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28438145/insights-into-the-availability-and-distribution-of-oral-artemisinin-monotherapy-in-myanmar-evidence-from-a-nationally-representative-outlet-survey
#3
Si Thu Thein, Hnin Su Su Khin, Aung Thi
BACKGROUND: The containment of artemisinin resistance in Myanmar, historically an important probable origin and route of anti-malarial resistance to the India sub-continent and beyond, is crucial to global malaria control and elimination. This paper describes what is currently known about the sale and distribution of oral artemisinin monotherapy (AMT) across Myanmar, where this medicine is commonly found. METHODS: A nationally representative 2015 outlet survey was conducted in the private sector, and among community health workers across four geographical domains...
April 25, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28427418/immunity-as-a-predictor-of-anti-malarial-treatment-failure-a-systematic-review
#4
Katherine O'Flaherty, Julia Maguire, Julie A Simpson, Freya J I Fowkes
BACKGROUND: Naturally acquired immunity can reduce parasitaemia and potentially influence anti-malarial treatment outcomes; however, evidence for this in the current literature provides conflicted results. The available evidence was synthesized to determine and quantify the association between host immunity and anti-malarial treatment failure. METHODS: Four databases were searched to identify studies investigating malaria antibody levels in patients receiving anti-malarial treatment for symptomatic malaria with treatment failure recorded according to the World Health Organization classification...
April 20, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28427409/efficacies-of-dha-ppq-and-as-sp-in-patients-with-uncomplicated-plasmodium-falciparum-malaria-in-an-area-of-an-unstable-seasonal-transmission-in-sudan
#5
Abdelrahim O Mohamed, Muzamil M Abdel Hamid, Omer S Mohamed, Nuha S Elkando, Abdelmaroof Suliman, Mariam A Adam, Fahad Awad Ali Elnour, Elfatih M Malik
BACKGROUND: Artemisinin-based combination therapy (ACT), together with other control measures, have reduced the burden of falciparum malaria in sub-Saharan countries, including Sudan. Sudan adopted ACT in 2004 with a remarkable reduction in mortality due to falciparum malaria. However, emergence of resistance to the first-line treatment artesunate and sulfadoxine/pyrimethamine (AS/SP) has created new challenges to the control of malaria in Sudan. A search for an alternative drug of choice for treating uncomplicated malaria has become inevitable...
April 20, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28420403/molecular-surveillance-of-plasmodium-falciparum-drug-resistance-in-the-republic-of-congo-four-and-nine-years-after-the-introduction-of-artemisinin-based-combination-therapy
#6
Felix Koukouikila-Koussounda, Sankarganesh Jeyaraj, Christian N Nguetse, Charles Nchotebah Nkonganyi, Kossiwa Clarisse Kokou, Mandingha K Etoka-Beka, Francine Ntoumi, Thirumalaisamy P Velavan
BACKGROUND: Resistance to anti-malarial drugs hinders efforts on malaria elimination and eradication. Following the global spread of chloroquine-resistant parasites, the Republic of Congo adopted artemisinin-based combination therapy (ACT) in 2006 as a first-line treatment for uncomplicated malaria. To assess the impacts after implementation of ACT, a molecular surveillance for anti-malarial drug resistance was conducted in Congo 4 and 9 years after the introduction of ACT. METHODS: Blood samples of 431 febrile children aged 1-10 years were utilized from two previous studies conducted in 2010 (N = 311) and 2015 (N = 120)...
April 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28410610/an-intricate-case-of-multidrug-resistant-plasmodium-falciparum-isolate-imported-from-cambodia
#7
Raffaele Dell'Acqua, Claudia Fabrizio, Francesco Di Gennaro, Sergio Lo Caputo, Annalisa Saracino, Michela Menegon, Mariangela L'Episcopia, Carlo Severini, Laura Monno, Francesco Castelli, Gioacchino Angarano
BACKGROUND: Imported cases of multidrug resistant Plasmodium falciparum and treatment failure with artemisinin-based regimens, although rare, have been described also in Western countries and their management is often challenging. This is also due to an inadequate knowledge and implementation of health prevention measures. CASE REPORT: A complex case of imported malaria caused by Plasmodium vivax/P. falciparum isolates in a patient who was not taking chemoprophylaxis while he was travelling in Cambodia is reported in this article...
April 14, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28407772/the-end-of-a-dogma-the-safety-of-doxycycline-use-in-young-children-for-malaria-treatment
#8
REVIEW
Tiphaine Gaillard, Sébastien Briolant, Marylin Madamet, Bruno Pradines
Anti-malarial drug resistance to chloroquine and sulfadoxine-pyrimethamine has spread from Southeast Asia to Africa. Furthermore, the recent emergence of resistance to artemisinin-based combination therapy (ACT) in Southeast Asia highlights the need to identify new anti-malarial drugs. Doxycycline is recommended for malaria chemoprophylaxis for travel in endemic areas, or in combination with the use of quinine for malaria treatment when ACT is unavailable or when the treatment of severe malaria with artesunate fails...
April 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28402391/the-relative-effects-of-artemether-lumefantrine-and-non-artemisinin-antimalarials-on-gametocyte-carriage-and-transmission-of-plasmodium-falciparum-a-systematic-review-and-meta-analysis
#9
Matthew M Ippolito, Julia Johnson, Christopher Mullin, Christopher Mallow, Nadia Morgan, Erika Wallender, Tianjing Li, Philip J Rosenthal
Background.: Artemisinin-based combination therapies (ACTs) have been widely adopted as first-line agents to treat uncomplicated falciparum malaria due to their activity against multidrug resistant parasites. ACTs may also disrupt transmission through a direct antigametocyte effect, but the extent of this effect is uncertain. We assessed the evidence for and estimated the effects of the most widely deployed ACT, artemether-lumefantrine (AL), relative to non-ACTs on gametocyte clearance and transmission interruption...
April 11, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28400526/plasmodium-falciparum-k13-mutations-differentially-impact-ozonide-susceptibility-and-parasite-fitness-in-vitro
#10
Judith Straimer, Nina F Gnädig, Barbara H Stokes, Michelle Ehrenberger, Audrey A Crane, David A Fidock
The emergence and spread in Southeast Asia of Plasmodium falciparum resistance to artemisinin (ART) derivatives, the cornerstone of first-line artemisinin-based combination therapies (ACTs), underscore the urgent need to identify suitable replacement drugs. Discovery and development efforts have identified a series of ozonides with attractive chemical and pharmacological properties that are being touted as suitable replacements. Partial resistance to ART, defined as delayed parasite clearance in malaria patients treated with an ART derivative or an ACT, has been associated with mutations in the P...
April 11, 2017: MBio
https://www.readbyqxmd.com/read/28388902/therapeutic-efficacy-and-artemisinin-resistance-in-northern-myanmar-evidence-from-in-vivo-and-molecular-marker-studies
#11
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
https://www.readbyqxmd.com/read/28384505/the-vivax-surveyor-online-mapping-database-for-plasmodium-vivax-clinical-trials
#12
REVIEW
R J Commons, K Thriemer, G Humphreys, I Suay, C H Sibley, P J Guerin, R N Price
INTRODUCTION: Recurrent P. vivax infections are associated with significant morbidity and mortality. Although radical cure can reduce recurrent infection, it is confounded by antimalarial resistance and the lack of safe and effective hypnozoitocidal treatment. This study documents the available literature of published clinical trials of P. vivax, providing an up to date, online, open access tool to view and download available information. METHODS: A systematic review was conducted according to PRISMA guidelines to identify prospective P...
March 24, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28372588/prolonged-parasite-clearance-in-a-chinese-splenectomized-patient-with-falciparum-malaria-imported-from-nigeria
#13
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
https://www.readbyqxmd.com/read/28368494/multi-omics-based-identification-of-specific-biochemical-changes-associated-with-pfkelch13-mutant-artemisinin-resistant-plasmodium-falciparum
#14
Ghizal Siddiqui, Anubhav Srivastava, Adrian S Russell, Darren J Creek
Background.: The emergence of artemisinin resistance in the malaria parasite, Plasmodium falciparum, poses a major threat to the control and elimination of malaria. Certain point mutations in the propeller domain of PfKelch13 are associated with resistance, but PfKelch13 mutations do not always result in clinical resistance. The underlying mechanisms associated with artemisinin resistance are poorly understood and the impact of PfKelch13 mutations on cellular biochemistry is not defined...
March 27, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28366726/cancer-combination-therapies-with-artemisinin-type-drugs
#15
REVIEW
Thomas Efferth
Artemisia annua L. is a Chinese medicinal plant, which is used throughout Asia and Africa as tea or press juice to treat malaria. The bioactivity of its chemical constituent, artemisinin is, however, much broader. We and others found that artemisinin and its derivatives also exert profound activity against tumor cells in vitro and in vivo. Should artemisinin-type drugs be applied routinely in clinical oncology in the future, then it should probably be as part of combination therapy regimens rather than as monotherapy...
March 31, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28361857/artemisinin-modulating-effect-on-human-breast-cancer-cell-lines-with-different-sensitivity-to-cytostatics
#16
V F Chekhun, N Yu Lukianova, T V Borikun, T V Zadvorny, A Mokhir
AIM: To explore effects of Artemisinin on a series of breast cancer cells with different sensitivity to typical cytotoxic drugs (doxorubicin - Dox; cisplatin - DDP) and to investigate possible artemisinin-induced modification of the mechanisms of drug resistance. MATERIALS AND METHODS: The study was performed on wild-type breast cancer MCF-7 cell line (MCF-7/S) and its two sublines MCF-7/Dox and MCF-7/DDP resistant to Dox and DDP, respectively. The cells were treated with artemisinin and iron-containing magnetic fluid...
March 2017: Experimental Oncology
https://www.readbyqxmd.com/read/28357581/malaria-an-update
#17
REVIEW
Srikanta Basu, Puneet Kaur Sahi
India is endemic for malaria with unstable transmission inhibiting the development of immunity and predisposing all age groups to the disease. Children under five are the greatest sufferers with maximum mortality. P. falciparum and P. vivax cause majority of cases. Fever is the cardinal symptom, though no set of signs and symptoms reliably distinguishes malaria from other causes of fever. In all suspected cases parasitological diagnosis should be confirmed before starting the treatment. Microscopy of blood smears is the gold standard for diagnosis...
March 30, 2017: Indian Journal of Pediatrics
https://www.readbyqxmd.com/read/28357359/chemical-proteomics-approach-reveals-the-direct-targets-and-the-heme-dependent-activation-mechanism-of-artemisinin-in-plasmodium-falciparum-using-an-artemisinin-based-activity-probe
#18
COMMENT
Jigang Wang, Qingsong Lin
Artemisinin and its analogues are currently the most effective anti-malarial drugs. The activation of artemisinin requires the cleavage of the endoperoxide bridge in the presence of iron sources. Once activated, artemisinins attack macromolecules through alkylation and propagate a series of damages, leading to parasite death. Even though several parasite proteins have been reported as artemisinin targets, the exact mechanism of action (MOA) of artemisinin is still controversial and its high potency and specificity against the malaria parasite could not be fully accounted for...
April 5, 2016: Microbial Cell
https://www.readbyqxmd.com/read/28355493/pfmdr1-plasmodium-falciparum-multidrug-drug-resistance-gene-1-a-pivotal-factor-in-malaria-resistance-to-artemisinin-combination-therapies
#19
J Pedro Gil, S Krishna
Plasmodium falciparum, the deadly agent of malaria, is notorious for its capacity to develop drug resistance. Treatment failures of artemisinin therapy regimens (ACTc), the present mainstay, is emerging. The transporter coding pfmdr1 gene is a central node in this process, having been associated with in vitro and in vivo parasite response to a broad range of ACT antimalarials. Areas covered: The review covers the historical origins of the pfmdr1 discovery, followed by a detailed description of its sequence and expression characteristics, as well as the structural and functional characteristics of its coded transmembrane protein...
April 10, 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28351924/plasmodium-falciparum-maf1-confers-survival-upon-amino-acid-starvation
#20
Kyle Jarrod McLean, Marcelo Jacobs-Lorena
The target of rapamycin complex 1 (TORC1) pathway is a highly conserved signaling pathway across eukaryotes that integrates nutrient and stress signals to regulate the cellular growth rate and the transition into and maintenance of dormancy. The majority of the pathway's components, including the central TOR kinase, have been lost in the apicomplexan lineage, and it is unknown how these organisms detect and respond to nutrient starvation in its absence. Plasmodium falciparum encodes a putative ortholog of the RNA polymerase (Pol) III repressor Maf1, which has been demonstrated to modulate Pol III transcription in a TOR-dependent manner in a number of organisms...
March 28, 2017: MBio
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