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Sarah G Staedke, Catherine Maiteki-Sebuguzi, Andrea M Rehman, Simon P Kigozi, Samuel Gonahasa, Jaffer Okiring, Steve W Lindsay, Moses R Kamya, Clare I R Chandler, Grant Dorsey, Chris Drakeley
BACKGROUND: Intermittent preventive treatment (IPT) is a well established malaria control intervention. Evidence that delivering IPT to schoolchildren could provide community-level benefits is limited. We did a cluster-randomised controlled trial to assess the effect of IPT of primary schoolchildren with dihydroartemisinin-piperaquine (DP) on indicators of malaria transmission in the community, in Jinja, Uganda. METHODS: We included 84 clusters, each comprising one primary school and the 100 closest available households...
April 13, 2018: Lancet Global Health
Yinxian Yang, Hailing Gao, Shanshan Hou, Ruijuan Su, Hongzh Uo Liu, Jin Sun
A quick and sensitive supercritical fluid chromatography with tandem mass spectrometry method for the simultaneous determination of lumefantrine, artemether and its active metabolite dihydroartemisinin in rat plasma was developed and validated. The chromatographic separation was performed on an ACQUITY UPC2 ™ BEH 2-EP column within 2.5 min by gradient elution using compressed CO2 and methanol containing 2 mM ammonium acetate as the mobile phases. Detection was achieved by multiple reaction monitoring using electrospray ionization in the positive ionization mode...
April 16, 2018: Journal of Separation Science
Haonan Yu, Zhuang Hou, Ye Tian, Yanhua Mou, Chun Guo
To develop novel agents with anticancer activities, thirty-four new dihydroartemisinin-coumarin hybrids were designed and synthesized in this study. Those compounds were identified that had great anticancer activity against two cancer cell lines (MDA-MB-231 and HT-29). The structure-activity relationships of the derivatives were also discussed, and the results of docking analysis had shown that carbonic anhydrases IX (CA IX) was very likely to be one of the drug targets of the hybrids. Meanwhile, to clarify the mechanism of the anticancer activity of the hybrids molecule, we did further exploration in the bioactivity of the hybrids...
April 3, 2018: European Journal of Medicinal Chemistry
Elizabeth Davlantes, Pedro Rafael Dimbu, Carolina Miguel Ferreira, Maria Florinda Joao, Dilunvuidi Pode, Jacinto Félix, Edgar Sanhangala, Benjamin Nieto Andrade, Samaly Dos Santos Souza, Eldin Talundzic, Venkatachalam Udhayakumar, Chantelle Owens, Eliane Mbounga, Lubbe Wiesner, Eric S Halsey, José Franco Martins, Filomeno Fortes, Mateusz M Plucinski
BACKGROUND: The Angolan government recommends three artemisinin-based combinations for the treatment of uncomplicated Plasmodium falciparum malaria: artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), and dihydroartemisinin-piperaquine (DP). Due to the threat of emerging anti-malarial drug resistance, it is important to periodically monitor the efficacy of artemisinin-based combination therapy (ACT). This study evaluated these medications' therapeutic efficacy in Benguela, Lunda Sul, and Zaire Provinces...
April 3, 2018: Malaria Journal
(no author information available yet)
BACKGROUND: Artemether-lumefantrine and artesunate-amodiaquine are used as first-line artemisinin-based combination therapies (ACTs) in west Africa. Pyronaridine-artesunate and dihydroartemisinin-piperaquine are potentially useful for diversification of ACTs in this region, but further safety and efficacy data are required on malaria retreatment. METHODS: We did a randomised, multicentre, open-label, longitudinal, controlled phase 3b/4 clinical trial at seven tertiary centres in Burkina Faso, Guinea, and Mali...
March 29, 2018: Lancet
Menno R Smit, Eric O Ochomo, Ghaith Aljayyoussi, Titus K Kwambai, Bernard O Abong'o, Tao Chen, Teun Bousema, Hannah C Slater, David Waterhouse, Nabie M Bayoh, John E Gimnig, Aaron M Samuels, Meghna R Desai, Penelope A Phillips-Howard, Simon K Kariuki, Duolao Wang, Steve A Ward, Feiko O Ter Kuile
BACKGROUND: Ivermectin is being considered for mass drug administration for malaria due to its ability to kill mosquitoes feeding on recently treated individuals. However, standard, single doses of 150-200 μg/kg used for onchocerciasis and lymphatic filariasis have a short-lived mosquitocidal effect (<7 days). Because ivermectin is well tolerated up to 2000 μg/kg, we aimed to establish the safety, tolerability, and mosquitocidal efficacy of 3 day courses of high-dose ivermectin, co-administered with a standard malaria treatment...
March 27, 2018: Lancet Infectious Diseases
Lanfen Huo, Wenwen Wei, Shaoling Wu, Xindong Zhao, Chunting Zhao, Hongguo Zhao, Lingjie Sun
The effectiveness of therapy combining dihydroartemisinin (DHA) and small interfering RNA targeting Notch1 (siNotch1) in T-cell lymphoma remains unknown. The present study explored the potential and possible mechanisms of combined dihydroarteminin, and siNotch1 therapy for T-cell lymphoma. It was demonstrated that the viability rates of siRNA-DHA-treated cells was significantly suppressed in comparison with those in control cells, control siRNA cells, siRNA-treated cells and DHA-treated cells (P<0.01). Additionally, there was a significant increase in cell apoptosis of siRNA-DHA-treated cells in comparison with those of control cells, control siRNA cells, siRNA-treated cells, DHA-treated cells (P<0...
March 2018: Experimental and Therapeutic Medicine
Inge Sutanto, Ayleen Kosasih, Iqbal R F Elyazar, Deddy R Simanjuntak, Tri A Larasati, M Sopiyudin Dahlan, Isra Wahid, Ivo Mueller, Cristian Koepfli, Rita Kusriastuti, Asik Surya, Ferdinand J Laihad, William A Hawley, Frank H Collins, J Kevin Baird, Neil F Lobo
Background: Mass screening and treatment (MST) aims to reduce malaria risk in communities by identifying and treating infected without regard to illness. Methods: A cluster-randomized trial evaluated malaria incidence with and without MST. Clusters were randomized to three, two, or no MST interventions: MST3=6 clusters (156 households/670 individuals); MST2=5 clusters (89 households/423 individuals); and MST0=5 clusters (174 households/777 individuals). All clusters completed the study with 15 residents withdrawing...
March 22, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Tony Fröhlich, Friedrich Hahn, Lucid Belmudes, Maria Leidenberger, Oliver Friedrich, Barbara Kappes, Yohann Couté, Manfred Marschall, Svetlana B Tsogoeva
Generation of dimers, trimers and dendrimers of bioactive compounds is one of the most recent approaches for the discovery of new potent drug candidates. Herein we present the synthesis of new artemisinin derived dimers and dendrimers, which were investigated against malaria parasite Plasmodium falciparum 3D7 strain and human cytomegalovirus (HCMV). Dimer 7 was, with an EC50 value of 1.4 nM, the most active compound in terms of antimalarial efficacy and was even more effective than the standard drugs dihydroartemisinin (EC50 = 2...
March 23, 2018: Chemistry: a European Journal
Jesmin Permala Lohy Das, Myat P Kyaw, Myat H Nyunt, Khin Chit, Kyin H Aye, Moe M Aye, Mats O Karlsson, Martin Bergstrand, Joel Tarning
BACKGROUND: Artemisinins are the most effective anti-malarial drugs for uncomplicated and severe Plasmodium falciparum malaria. However, widespread artemisinin resistance in the Greater Mekong Region of Southeast Asia is threatening the possibility to control and eliminate malaria. This work aimed to evaluate the pharmacokinetic and pharmacodynamic properties of artesunate and its active metabolite, dihydroartemisinin, in patients with sensitive and resistant falciparum infections in Southern Myanmar...
March 23, 2018: Malaria Journal
Kazuyuki Maeda, Hinayo Ichikawa, Yuichi Nakajima, Takayuki Motoyama, Shuichi Ohsato, Kyoko Kanamaru, Tetsuo Kobayashi, Takumi Nishiuchi, Hiroyuki Osada, Makoto Kimura
From the RIKEN Natural Products Depository (NPDepo) chemical library, we identified small molecules that alter trichothecene 15-acetyldeoxynivalenol (15-ADON) production by Fusarium graminearum. Among trichothecene production activators, a furanocoumarin NPD12671 showed the strongest stimulatory activity on 15-ADON production by the fungus cultured in a 24-well plate. NPD12671 significantly increased the transcription of Tri6, a transcription factor gene necessary for trichothecene biosynthesis, in both trichothecene-inducing and non-inducing culture conditions...
March 22, 2018: ACS Chemical Biology
Rada M Savic, Prasanna Jagannathan, Richard Kajubi, Liusheng Huang, Nan Zhang, Moses Were, Abel Kakuru, Mary K Muhindo, Norah Mwebaza, Erika Wallender, Tamara D Clark, Bishop Opira, Moses Kamya, Diane V Havlir, Philip J Rosenthal, Grant Dorsey, Francesca T Aweeka
Background: Dihydroartemsinin-piperaquine is highly efficacious as intermittent preventive therapy for malaria during pregnancy (IPTp). Determining associations between piperaquine exposure, malaria risk, and adverse birth outcomes informs optimal dosing strategies. Methods: HIV-uninfected pregnant women were enrolled in a placebo-controlled trial of IPTp at 12-20 weeks gestation and randomized to: sulfadoxine-pyrimethamine every 8 weeks (n=106), dihydroartemsinin-piperaquine every 8 weeks (n=94), or dihydroartemsinin-piperaquine every 4 weeks (n=100) during pregnancy...
March 14, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Qiujun Liu, Xianyao Zhou, Chuan Li, Xuemei Zhang, Chang Long Li
There is limited knowledge regarding the influence of autophagy on the anticancer effect of dihydroartemisinin (DHA). The present study aimed to investigate this influence within human breast cancer cells. Changes in cell viability, cell cycle distribution, apoptosis and associated genes were analyzed in MDA-MB-231 cells subjected to DHA following alteration in autophagy levels; the autophagy level was decreased following autophagy-related 7 (Atg7) knockdown or increased using rapamycin. The data indicated that rapamycin had the ability to notably enhance the anticancer effect of DHA on MDA-MB-231 cells...
April 2018: Oncology Letters
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
Rupam Tripura, Thomas J Peto, Chea Nguon, Chan Davoeung, Mavuto Mukaka, Pasathorn Sirithiranont, Mehul Dhorda, Cholrawee Promnarate, Mallika Imwong, Lorenz von Seidlein, Jureeporn Duanguppama, Krittaya Patumrat, Huy Rekol, Martin P Grobusch, Nicholas P J Day, Nicholas J White, Arjen M Dondorp
Background: The increase in multidrug resistant Plasmodium falciparum in Southeast Asia suggests a need for acceleration of malaria elimination. We evaluated the effectiveness and safety of mass drug administrations (MDA) to interrupt malaria transmission. Methods: Four malaria-endemic villages in western Cambodia were randomized to three rounds of MDA (a three-day course of dihydroartemisinin with piperaquine-phosphate), administered in either early or at the end of the study-period...
March 7, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Harr-Keshauve Mungun, Shuzhen Li, Yue Zhang, Songming Huang, Zhanjun Jia, Guixia Ding, Aihua Zhang
Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin and has been used as an antimalarial drug. Recently, roles of artemisinin and its derivatives in treating diseases besides antimalarial effect were documented. Thus, this study was undertaken to investigate the role of DHA in indoxyl sulfate (IS)-promoted cell cycle progression in glomerular mesangial cells, as well as the potential mechanisms. Under the basal condition, DHA significantly retarded the cell cycle progression as shown by decreased cell percentage in S phase and increased cell percentage in G1/G0 phases in line with reduced cell cycle proteins cyclin A2 and cyclin D1...
2018: American Journal of Translational Research
Zhen-Hai Lu, Jian-Hong Peng, Rong-Xin Zhang, Fulong Wang, Hui-Ping Sun, Yu-Jing Fang, De-Sen Wan, Zhi-Zhong Pan
The present study was aimed to investigate the effect of dihydroartemisinin on the colon cancer cell proliferation and apoptosis. The results from MTT assay revealed a concentration and time dependent relation between the inhibition of SW 948 cell viability and dihydroartemisinin addition. The viability of SW 948 cells was reduced to 45 and 24% on treatment with 30 and 50 µM, respectively concentrations of dihydroartemisinin after 48 h. Morphological examination of SW 948 cells showed attainment of rounded shape and cluster formation on treatment with dihydroartemisinin...
February 2018: Saudi Journal of Biological Sciences
Kimberly F Breglio, Rifat S Rahman, Juliana M Sá, David J Roberts, Thomas E Wellems
Some Kelch mutations of Plasmodium falciparum K13 protein confer increased survival to dihydroartemisinin (DHA)-treated ring-stage parasites. Here, we ask if K13 mutations affect a dormancy phenotype allowing parasites to survive DHA exposure then sorbitol selection. Although recrudescence from dormancy differed between two distinct parasites lines, it was similar for isogenic lines carrying single-site substitutions in K13. Therefore, K13 mutations do not alter the DHA-sorbitol combined dormancy phenotype; traits from other loci likely determine this phenotype...
February 20, 2018: Antimicrobial Agents and Chemotherapy
Joseph Okebe, Joan Muela Ribera, Julie Balen, Fatou Jaiteh, Yoriko Masunaga, Davis Nwakanma, John Bradley, Shunmay Yeung, Koen Peeters Grietens, Umberto D'Alessandro
BACKGROUND: Systematic treatment of all individuals living in the same compound of a clinical malaria case may clear asymptomatic infections and possibly reduce malaria transmission, where this is focal. High and sustained coverage is extremely important and requires active community engagement. This study explores a community-based approach to treating malaria case contacts. METHODS/DESIGN: This is a cluster-randomized trial to determine whether, in low-transmission areas, treating individuals living in the same compound of a clinical malaria case with dihydroartemisinin-piperaquine can reduce parasite carriage and thus residual malaria transmission...
February 20, 2018: Trials
Jia-Tian Cao, Hui-Min Mo, Yue Wang, Kai Zhao, Tian-Tian Zhang, Chang-Qian Wang, Kai-Lin Xu, Zhi-Hua Han
Dihydroartemisinin (DHA) is a derivative of artemisinin. The present study aimed to investigate whether DHA induces apoptosis in the THP-1 human acute monocytic leukemia cell line (AMoL), and to identify the relative molecular mechanisms. The results of the present study demonstrated that the viability of THP-1 cells were inhibited by DHA in a dose- and time-dependent manner, which was accompanied by morphological characteristics associated with apoptosis. After 24 h of 200 µM DHA treatment, the proportion of apoptotic cells was significantly increased compared with the untreated controls (P<0...
March 2018: Oncology Letters
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