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Dihydroartemisinin

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https://www.readbyqxmd.com/read/27923947/short-term-impact-of-mass-drug-administration-with-dihydroartemisinin-plus-piperaquine-on-malaria-in-southern-province-zambia-a-cluster-randomized-controlled-trial
#1
Thomas P Eisele, Adam Bennett, Kafula Silumbe, Timothy P Finn, Victor Chalwe, Mulakwa Kamuliwo, Busiku Hamainza, Hawela Moonga, Emmanuel Kooma, Elizabeth Chizema Kawesha, Joshua Yukich, Joseph Keating, Travis Porter, Ruben O Conner, Duncan Earle, Richard W Steketee, John M Miller
BACKGROUND:  Mass drug administration (MDA) using dihydroartemisinin plus piperaquine (DHAp) represents a potential strategy to clear Plasmodium falciparum infections and reduce the human parasite reservoir. METHODS:  A cluster-randomized controlled trial in Southern Province, Zambia, was used to assess the short-term impact of 2 rounds of community-wide MDA and household-level (focal) MDA with DHAp compared with no mass treatment. Study end points included parasite prevalence in children, infection incidence, and confirmed malaria case incidence...
December 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27919892/significant-divergence-in-sensitivity-to-antimalarial-drugs-between-neighboring-plasmodium-falciparum-populations-along-the-eastern-border-of-myanmar
#2
Weilin Zeng, Yao Bai, Meilian Wang, Zenglei Wang, Shuang Deng, Yonghua Ruan, Shi Feng, Zhaoqing Yang, Liwang Cui
Malaria parasites in different endemic areas display different levels of resistance to antimalarial drugs as the result of varied drug use histories. To provide updated knowledge of drug sensitivities during the malaria elimination phase in Southeast Asia, an epicenter of multidrug resistance, we determined in vitro susceptibilities of culture-adapted Plasmodium falciparum isolates from two eastern border regions (Wa and Kachin) of Myanmar to ten drugs. Despite their close proximity, the Kachin parasites displayed higher IC50 values than the Wa parasites to chloroquine, piperaquine, naphthoquine, mefloquine, quinine, pyrimethamine, pyronaridine, lumefantrine and dihydroartemisinin...
December 5, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27903279/in-vitro-and-in-vivo-anti-malarial-activity-of-novel-harmine-analog-heat-shock-protein-90-inhibitors-a-possible-partner-for-artemisinin
#3
Abebe Genetu Bayih, Asongna Folefoc, Abu Naser Mohon, Scott Eagon, Marc Anderson, Dylan R Pillai
BACKGROUND: The emergence of artemisinin-resistant Plasmodium falciparum strains poses a serious challenge to the control of malaria. This necessitates the development of new anti-malarial drugs. Previous studies have shown that the natural beta-carboline alkaloid harmine is a promising anti-malarial agent targeting the P. falciparum heat-shock protein 90 (PfHsp90). The aim of this study was to test the anti-malarial activity of harmine analogues. METHODS: Forty-two harmine analogues were synthesized and the binding of these analogues to P...
December 1, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27900057/in-vitro-and-in-vivo-inhibition-of-tumor-cell-viability-by-combined-dihydroartemisinin-and-doxorubicin-treatment-and-the-underlying-mechanism
#4
Xiang Tai, Xiao-Bei Cai, Zhang Zhang, Rui Wei
The natural extract artemisinin and its derivatives have good anticancer activity. The present study aimed to investigate the in vitro inhibitory effects of combined dihydroartemisinin (DHA) and doxorubicin (DOX) treatment on a variety of tumor cell lines (HeLa, OVCAR-3, MCF-7, PC-3 and A549), as well as the underlying mechanisms. In addition, the in vivo effects of DHA and DOX were evaluated using a mouse HeLa tumor model. The HeLa, OVCAR-3, MCF-7, PC-3 and A549 cells were treated with a combination of DHA and DOX, and the effect on cell viability was detected by Cell Counting kit-8...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27896916/dihydroartemisinin-counteracts-fibrotic-portal-hypertension-via-farnesoid-x-receptor-dependent-inhibition-of-hepatic-stellate-cell-contraction
#5
Wenxuan Xu, Chunfeng Lu, Feng Zhang, Jiangjuan Shao, Shunyu Yao, Shizhong Zheng
Portal hypertension is a frequent pathological symptom occurring especially in hepatic fibrosis and cirrhosis. Current paradigms indicate that inhibition of hepatic stellate cell (HSC) activation and contraction is anticipated to be an attractive therapeutic strategy, because activated HSC dominantly facilitates an increase in intrahepatic vein pressure through secreting extracellular matrix and contracting. Our previous in vitro study indicated that dihydroartemisinin (DHA) inhibited contractility of cultured HSC by activating intracellular farnesoid X receptor (FXR)...
November 7, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27895848/four-artemisinin-based-treatments-in-african-pregnant-women-with-malaria
#6
Divine Pekyi, Akua A Ampromfi, Halidou Tinto, Maminata Traoré-Coulibaly, Marc C Tahita, Innocent Valéa, Victor Mwapasa, Linda Kalilani-Phiri, Gertrude Kalanda, Mwayiwawo Madanitsa, Raffaella Ravinetto, Theonest Mutabingwa, Prosper Gbekor, Harry Tagbor, Gifty Antwi, Joris Menten, Maaike De Crop, Yves Claeys, Celine Schurmans, Chantal Van Overmeir, Kamala Thriemer, Jean-Pierre Van Geertruyden, Umberto D'Alessandro, Michael Nambozi, Modest Mulenga, Sebastian Hachizovu, Jean-Bertin B Kabuya, Joyce Mulenga
BACKGROUND: Information regarding the safety and efficacy of artemisinin combination treatments for malaria in pregnant women is limited, particularly among women who live in sub-Saharan Africa. METHODS: We conducted a multicenter, randomized, open-label trial of treatments for malaria in pregnant women in four African countries. A total of 3428 pregnant women in the second or third trimester who had falciparum malaria (at any parasite density and regardless of symptoms) were treated with artemether-lumefantrine, amodiaquine-artesunate, mefloquine-artesunate, or dihydroartemisinin-piperaquine...
September 2016: Malawi Medical Journal: the Journal of Medical Association of Malawi
https://www.readbyqxmd.com/read/27895526/development-of-a-simple-and-specific-direct-competitive-elisa-for-the-determination-of-artesunate-using-an-anti-artesunate-polyclonal-antiserum
#7
Yoshinori Mitsui
BACKGROUND: Since artesunate (ART) became a vital component of artemisinin (ARM)-based combination therapies for the treatment for malaria, counterfeit ART drugs have spread in regions of Southeast Asia and Africa. The consumption of counterfeit ART drugs has resulted in the death of many patients. Thus, evaluating the quality of ART drugs is needed. There are several methods for quantitating the ART content in tablets, the most common being a high-performance liquid chromatography. However, that method is hampered by the need for expensive equipment and a rather time-consuming process of extraction...
2016: Tropical Medicine and Health
https://www.readbyqxmd.com/read/27895313/repurposing-the-anti-malarial-drug-dihydroartemisinin-suppresses-metastasis-of-non-small-cell-lung-cancer-via-inhibiting-nf-%C3%AE%C2%BAb-glut1-axis
#8
Jie Jiang, Guojun Geng, Xiuyi Yu, Hongming Liu, Jing Gao, Hanxiang An, Chengfu Cai, Ning Li, Dongyan Shen, Xiaoqiang Wu, Lisheng Zheng, Yanjun Mi, Shuyu Yang
Non-small-cell lung cancer (NSCLC) is an aggressive malignancy and long-term survival remains unsatisfactory for patients with metastatic and recurrent disease. Repurposing the anti-malarial drug dihydroartemisinin (DHA) has been proved to possess potent antitumor effect on various cancers. However, the effects of DHA in preventing the invasion of NSCLC cells have not been studied. In the present study, we determined the inhibitory effects of DHA on invasion and migration and the possible mechanisms involved using A549 and H1975 cells...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27895269/stability-of-dihydroartemisinin-piperaquine-tablet-halves-during-prolonged-storage-under-tropical-conditions
#9
Eva Maria Hodel, Harparkash Kaur, Dianne J Terlouw
Dihydroartemisinin-piperaquine (DP) is recommended for the treatment of uncomplicated malaria, used in efforts to contain artemisinin resistance, and increasingly considered for mass drug administration. Because of the narrow therapeutic dose range and available tablet strengths, the manufacturers and World Health Organization recommended regimens involve breaking tablets into halves to accurately dose children according to body weight. Use of tablet fractions in programmatic settings under tropical conditions requires a highly stable product; however, the stability of DP tablet fractions is unknown...
November 28, 2016: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27894353/provider-and-user-acceptability-of-intermittent-screening-and-treatment-for-the-control-of-malaria-in-pregnancy-in-malawi
#10
Deborah Almond, Mwayi Madanitsa, Victor Mwapasa, Linda Kalilani-Phiri, Jayne Webster, Feiko Ter Kuile, Lucy Paintain
BACKGROUND: Malaria in pregnancy is a major cause of adverse maternal and fetal outcomes. Intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) is one of the control strategies promoted by WHO. In response to mounting resistance to SP, intermittent screening and treatment (ISTp) has been proposed as an alternative. The objective of this study was to explore the acceptability of ISTp for health workers and pregnant women. METHODS: Semi-structured interviews of ten health workers and five focus group discussions of 38 women enrolled in an ongoing trial comparing IPTp-SP and ISTp with dihydroartemisinin-piperaquine (DP) were conducted at two antenatal clinics in rural Malawi...
November 28, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27887614/insight-into-k13-propeller-gene-polymorphism-and-ex-vivo-dha-response-profiles-from-cameroonian-isolates
#11
Sandie Menard, Joëlle Njila Tchoufack, Christelle Ngou Maffo, Sandrine E Nsango, Xavier Iriart, Luc Abate, Majoline Tchioffo Tsapi, Parfait H Awono-Ambéné, Francis A Abega Mekongo, Isabelle Morlais, Antoine Berry
BACKGROUND: The spread of Plasmodium falciparum resistance to artemisinin derivatives in Southeast Asia is a major source of concern and the emergence of resistance in Africa would have dramatic consequences, by increasing malaria mortality and morbidity. It is therefore urgent to implement regular monitoring in sentinel sites in sub-Saharan Africa using robust and easy-to-implement tools. The prevalence of k13-propeller mutations and the phenotypic profiles are poorly known in sub-Saharan Africa...
November 26, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27869748/design-of-new-antibacterial-enhancers-based-on-acrb-s-structure-and-the-evaluation-of-their-antibacterial-enhancement-activity
#12
Yi Song, Rongxin Qin, Xichun Pan, Qin Ouyang, Tianyu Liu, Zhaoxia Zhai, Yingchun Chen, Bin Li, Hong Zhou
Previously, artesunate (AS) and dihydroartemisinine 7 (DHA7) were found to have antibacterial enhancement activity against Escherichia coli via inhibition of the efflux pump AcrB. However, they were only effective against E. coli standard strains. This study aimed to develop effective antibacterial enhancers based on the previous work. Our results demonstrate that 86 new antibacterial enhancers were designed via 3D-SAR and molecular docking. Among them, DHA27 had the best antibacterial enhancement activity...
November 18, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27865892/dihydroartemisinin-piperaquine-if-it-works-for-control-can-we-use-it-for-elimination
#13
Quique Bassat, Clara Menéndez
No abstract text is available yet for this article.
November 16, 2016: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/27865890/safety-tolerability-and-efficacy-of-repeated-doses-of-dihydroartemisinin-piperaquine-for-prevention-and-treatment-of-malaria-a-systematic-review-and-meta-analysis
#14
Julie Gutman, Stephanie Kovacs, Grant Dorsey, Andy Stergachis, Feiko O Ter Kuile
BACKGROUND: Intermittent preventive treatment (IPT) for malaria is used in infants, children, adults, and pregnant women. Dihydroartemisinin-piperaquine (DP) is an effective, well tolerated artemisinin-based combination therapy. The long half-life of piperaquine makes it attractive for IPT. We conducted a systematic review and meta-analysis to establish the efficacy and safety of repeated treatment with DP. METHODS: Following PRISMA guidelines, we searched multiple databases on Sept 1, 2016, with the terms: "human" AND "dihydroartemisinin-piperaquine" OR "DHA-PPQ"...
November 16, 2016: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/27856406/efficacy-and-safety-of-high-dose-ivermectin-for-reducing-malaria-transmission-ivermal-protocol-for-a-double-blind-randomized-placebo-controlled-dose-finding-trial-in-western-kenya
#15
Menno R Smit, Eric Ochomo, Ghaith Aljayyoussi, Titus Kwambai, Bernard Abong'o, Nabie Bayoh, John Gimnig, Aaron Samuels, Meghna Desai, Penelope A Phillips-Howard, Simon Kariuki, Duolao Wang, Steve Ward, Feiko O Ter Kuile
BACKGROUND: Innovative approaches are needed to complement existing tools for malaria elimination. Ivermectin is a broad spectrum antiparasitic endectocide clinically used for onchocerciasis and lymphatic filariasis control at single doses of 150 to 200 mcg/kg. It also shortens the lifespan of mosquitoes that feed on individuals recently treated with ivermectin. However, the effect after a 150 to 200 mcg/kg oral dose is short-lived (6 to 11 days). Modeling suggests higher doses, which prolong the mosquitocidal effects, are needed to make a significant contribution to malaria elimination...
November 17, 2016: JMIR Research Protocols
https://www.readbyqxmd.com/read/27835669/the-glutaminase-1-inhibitor-968-enhances-dihydroartemisinin-mediated-antitumor-efficacy-in-hepatocellular-carcinoma-cells
#16
Diancheng Wang, Gang Meng, Meihong Zheng, Yonghui Zhang, Aiping Chen, Junhua Wu, Jiwu Wei
Reprogrammed metabolism and redox homeostasis are potential targets of cancer therapy. Our previous study demonstrated that the kidney form of glutaminase (GLS1) is highly expressed in hepatocellular carcinoma (HCC) cells and can be used as a target for effective anticancer therapy. Dihydroartemisinin (DHA) increases intracellular reactive oxygen species (ROS) levels leading to cytotoxicity in cancer cells. However, the heterogeneity of cancer cells often leads to differing responses to oxidative lesions. For instance, cancer cells with high ratio of GSH/GSSG, a critical ROS scavenger, are resistant to ROS-induced cytotoxicity...
2016: PloS One
https://www.readbyqxmd.com/read/27825738/the-gametocytocidal-efficacy-of-different-single-doses-of-primaquine-with-dihydroartemisinin-piperaquine-in-asymptomatic-parasite-carriers-in-the-gambia-a-randomized-controlled-trial
#17
Joseph Okebe, Teun Bousema, Muna Affara, Gian Luca Di Tanna, Edgard Dabira, Abdoulaye Gaye, Frank Sanya-Isijola, Henry Badji, Simon Correa, Davis Nwakanma, Jean-Pierre Van Geertruyden, Chris Drakeley, Umberto D'Alessandro
BACKGROUND: Asymptomatic low-density gametocyte carriers represent the majority of malaria-infected individuals. However, the impact of recommended treatment with single low dose of primaquine and an artemisinin-based combination therapy to reduce transmission in this group is unknown. METHODS: This was a four-arm, open label, randomized controlled trial comparing the effect of dihydroartemisinin-piperaquine (DHAP) alone or combined with single dose of primaquine (PQ) at 0...
October 23, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27821127/treatment-seeking-behaviour-and-associated-costs-for-malaria-in-papua-indonesia
#18
Muhammad Karyana, Angela Devine, Enny Kenangalem, Lenny Burdarm, Jeanne Rini Poespoprodjo, Ram Vemuri, Nicholas M Anstey, Emiliana Tjitra, Ric N Price, Shunmay Yeung
BACKGROUND: Malaria remains a significant public health issue in Eastern Indonesia, where multidrug resistant Plasmodium falciparum and Plasmodium vivax are highly prevalent. The objective of this study was to describe treatment-seeking behaviour and household costs prior to a change to a unified treatment policy of dihydroartemisinin-piperaquine in Mimika district, Papua province in 2006. METHODS: In 2005 a randomized cross-sectional household survey was conducted to collect data on demographics, socio-economic status (SES), treatment-seeking, case management, and household costs...
November 8, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27818097/a-surrogate-marker-of-piperaquine-resistant-plasmodium-falciparum-malaria-a-phenotype-genotype-association-study
#19
Benoit Witkowski, Valentine Duru, Nimol Khim, Leila S Ross, Benjamin Saintpierre, Johann Beghain, Sophy Chy, Saorin Kim, Sopheakvatey Ke, Nimol Kloeung, Rotha Eam, Chanra Khean, Malen Ken, Kaknika Loch, Anthony Bouillon, Anais Domergue, Laurence Ma, Christiane Bouchier, Rithea Leang, Rekol Huy, Grégory Nuel, Jean-Christophe Barale, Eric Legrand, Pascal Ringwald, David A Fidock, Odile Mercereau-Puijalon, Frédéric Ariey, Didier Ménard
BACKGROUND: Western Cambodia is the epicentre of Plasmodium falciparum multidrug resistance and is facing high rates of dihydroartemisinin-piperaquine treatment failures. Genetic tools to detect the multidrug-resistant parasites are needed. Artemisinin resistance can be tracked using the K13 molecular marker, but no marker exists for piperaquine resistance. We aimed to identify genetic markers of piperaquine resistance and study their association with dihydroartemisinin-piperaquine treatment failures...
November 3, 2016: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/27818095/genetic-markers-associated-with-dihydroartemisinin-piperaquine-failure-in-plasmodium-falciparum-malaria-in-cambodia-a-genotype-phenotype-association-study
#20
Roberto Amato, Pharath Lim, Olivo Miotto, Chanaki Amaratunga, Dalin Dek, Richard D Pearson, Jacob Almagro-Garcia, Aaron T Neal, Sokunthea Sreng, Seila Suon, Eleanor Drury, Dushyanth Jyothi, Jim Stalker, Dominic P Kwiatkowski, Rick M Fairhurst
BACKGROUND: As the prevalence of artemisinin-resistant Plasmodium falciparum malaria increases in the Greater Mekong subregion, emerging resistance to partner drugs in artemisinin combination therapies seriously threatens global efforts to treat and eliminate this disease. Molecular markers that predict failure of artemisinin combination therapy are urgently needed to monitor the spread of partner drug resistance, and to recommend alternative treatments in southeast Asia and beyond. METHODS: We did a genome-wide association study of 297 P falciparum isolates from Cambodia to investigate the relationship of 11 630 exonic single-nucleotide polymorphisms (SNPs) and 43 copy number variations (CNVs) with in-vitro piperaquine 50% inhibitory concentrations (IC50s), and tested whether these genetic variants are markers of treatment failure with dihydroartemisinin-piperaquine...
November 3, 2016: Lancet Infectious Diseases
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