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chloroquine resistance

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https://www.readbyqxmd.com/read/27919892/significant-divergence-in-sensitivity-to-antimalarial-drugs-between-neighboring-plasmodium-falciparum-populations-along-the-eastern-border-of-myanmar
#1
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/27919256/the-return-of-chloroquine-susceptible-plasmodium-falciparum-malaria-in-zambia
#2
Sydney Mwanza, Sudhaunshu Joshi, Michael Nambozi, Justin Chileshe, Phidelis Malunga, Jean-Bertin Bukasa Kabuya, Sebastian Hachizovu, Christine Manyando, Modest Mulenga, Miriam Laufer
BACKGROUND: Plasmodium falciparum resistance to anti-malarial drugs remains a major obstacle to malaria control and elimination. The parasite has developed resistance to every anti-malarial drug introduced for wide-scale treatment. However, the spread of resistance may be reversible. Malawi was the first country to discontinue chloroquine use due to widespread resistance. Within a decade of the removal of drug pressure, the molecular marker of chloroquine-resistant malaria had disappeared and the drug was shown to have excellent clinical efficacy...
December 5, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27914754/antiparasitic-and-disease-modifying-activity-of-nyctanthes-arbor-tristis-linn-in-malaria-an-exploratory-clinical-study
#3
Chhaya S Godse, Prakash S Tathed, Sameer S Talwalkar, Rama A Vaidya, Ashok J Amonkar, Akhil B Vaidya, Ashok D B Vaidya
BACKGROUND: An unceasing threat of drug resistance continuously poses demand for new antimalarial drugs. A scientific assessment of traditionally used antimalarial plants through reverse pharmacology is crucial for a fast track drug discovery. An Ayurvedic plant Nyctanthesarbor-tristis Linn. - (Parijat) had shown antimalarial activity, with a parasite clearance in 76.6% of 120 patients, in an earlier clinical study. OBJECTIVE: To further explore antimalarial potential of the plant through additional objective markers...
November 30, 2016: Journal of Ayurveda and Integrative Medicine
https://www.readbyqxmd.com/read/27910983/investigation-and-intervention-of-autophagy-to-guide-cancer-treatment-with-nanogels
#4
Xudong Zhang, Xin Liang, Jianjun Gu, Danfeng Chang, Jinxie Zhang, Zhaowei Chen, Yanqi Ye, Chao Wang, Wei Tao, Xiaowei Zeng, Gan Liu, Yongjun Zhang, Lin Mei, Zhen Gu
Cancer cells use autophagy to resist poor survival environmental conditions such as low PH, poor nutrients as well as chemical therapy. Nanogels have been used as efficient chemical drug carriers for cancer treatment. However, the effect of nanogels on autophagy is still unknown. Here, we used Rab proteins as the marker of multiple trafficking vesicles in endocytosis and LC3 as the marker of autophagy to investigate the intracellular trafficking network of Rhodamine B (Rho)-labeled nanogels. The nanogels were internalized by the cells through multiple protein dependent endocytosis and micropinocytosis...
December 2, 2016: Nanoscale
https://www.readbyqxmd.com/read/27899115/characterizing-the-impact-of-sustained-sulfadoxine-pyrimethamine-use-upon-the-plasmodium-falciparum-population-in-malawi
#5
Matt Ravenhall, Ernest Diez Benavente, Mwapatsa Mipando, Anja T R Jensen, Colin J Sutherland, Cally Roper, Nuno Sepúlveda, Dominic P Kwiatkowski, Jacqui Montgomery, Kamija S Phiri, Anja Terlouw, Alister Craig, Susana Campino, Harold Ocholla, Taane G Clark
BACKGROUND: Malawi experienced prolonged use of sulfadoxine/pyrimethamine (SP) as the front-line anti-malarial drug, with early replacement of chloroquine and delayed introduction of artemisinin-based combination therapy. Extended use of SP, and its continued application in pregnancy is impacting the genomic variation of the Plasmodium falciparum population. METHODS: Whole genome sequence data of P. falciparum isolates covering 2 years of transmission within Malawi, alongside global datasets, were used...
November 29, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27896925/design-synthesis-and-in-vitro-antiplasmodial-activity-of-some-bisquinolines-against-chloroquine-resistant-strain
#6
Srinivasarao Kondaparla, Pooja Agarwal, Kumkum Srivastava, Sunil K Puri, S B Katti
A series of novel bisquinoline compounds comprising, N(1) -(7-chloroquinolin-4-yl) ethane-1,2-diamine and 7-chloro-N-(2-(piperazin-1-yl)ethyl)quinolin-4-amine connected with 7-chloro-4-aminoquinoline containing various amino acids is described. We have bio-evaluated the compounds against both chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum in vitro. Among the series, compounds 4 and 7 exhibited 1.8 and 10.6 fold superior activity as compared to chloroquine (CQ) (IC50 = 0...
November 29, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27895479/cationic-pegylated-liposomes-incorporating-an-antimicrobial-peptide-tilapia-hepcidin-2-3-an-adjuvant-of-epirubicin-to-overcome-multidrug-resistance-in-cervical-cancer-cells
#7
Vivian Juang, Hsin-Pin Lee, Anya Maan-Yuh Lin, Yu-Li Lo
Antimicrobial peptides (AMPs) have been recently evaluated as a new generation of adjuvants in cancer chemotherapy. In this study, we designed PEGylated liposomes encapsulating epirubicin as an antineoplastic agent and tilapia hepcidin 2-3, an AMP, as a multidrug resistance (MDR) transporter suppressor and an apoptosis/autophagy modulator in human cervical cancer HeLa cells. Cotreatment of HeLa cells with PEGylated liposomal formulation of epirubicin and hepcidin 2-3 significantly increased the cytotoxicity of epirubicin...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27867537/aquaporin-3-facilitates-chemoresistance-in-gastric-cancer-cells-to-cisplatin-via-autophagy
#8
Xuqiang Dong, Yao Wang, Yangchun Zhou, Jianfei Wen, Shoulin Wang, Lizong Shen
Cisplatin (cDDP) remains one of the first-line chemotherapeutic agents for gastric cancer (GC) treatment, and resistance to cDDP is the major limitation in its clinical application. Mechanisms of cDDP resistance have been shown to be varied and complicated. Aquaporin 3 (AQP3) has been demonstrated to be overexpressed in GC tissues and is thought to be involved in GC carcinogenesis and progression. However, the role of AQP3 in chemosensitivity of GC to cytotoxic agents remains unknown. In this study, we show that AQP3 overexpression induced resistance to cDDP in AGS cells (P<0...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27866919/in-vitro-sensitivity-of-antimalarial-drugs-and-correlation-with-clinico-parasitological-response-following-treatment-with-a-3-day-artesunate-mefloquine-combination-in-patients-with-falciparum-malaria-along-the-thai-myanmar-border
#9
Phunuch Muhamad, Artitaya Thiengsusuk, Papichaya Phompradit, Kesara Na-Bangchang
A 3-day artesunate-mefloquine combination therapy has been using as first-line treatment for acute uncomplicated Plasmodium falciparum malaria in Thailand since 1995 on the background of mefloquine resistance. The aim of the present study was to assess sensitivity of P. falciparum isolates (n=44) in an area along the Thai-Myanmar border (year 2009) to artesunate, mefloquine, chloroquine and quinine, including their correlation with clinico-parasitological response. Twenty, 19, and 5 isolates were collected from patients with 'Adequate Clinical and Parasitological Response (ACPR)', 'Late Parasitological Failure (LPF)' and 're-infection', respectively...
November 17, 2016: Acta Tropica
https://www.readbyqxmd.com/read/27863375/h2o2-treatment-or-serum-deprivation-induces-autophagy-and-apoptosis-in-naked-mole-rat-skin-fibroblasts-by-inhibiting-the-pi3k-akt-signaling-pathway
#10
Shanmin Zhao, Li Li, Shiyong Wang, Chenlin Yu, Bang Xiao, Lifang Lin, Wei Cong, Jishuai Cheng, Wenjing Yang, Wei Sun, Shufang Cui
Naked mole-rats (NMR; Heterocephalus glaber) display extreme longevity and resistance to cancer. Here, we examined whether autophagy contributes to the longevity of NMRs by assessing the effects of the PI3K/Akt pathway inhibitor LY294002 and the autophagy inhibitor chloroquine (CQ) on autophagy and apoptosis in NMR skin fibroblasts. Serum starvation, H2O2 treatment, and LY294002 treatment all increased the LC3-II/LC3-I ratio and numbers of double-membraned autophagosomes and autophagic vacuoles, and decreased levels of p70S6K, p-AktSer473, and p-AktThr308...
November 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27861509/parasitological-clearance-rates-and-drug-concentrations-of-a-fixed-dose-combination-of-azithromycin-chloroquine-in-asymptomatic-pregnant-women-with-plasmodium-falciparum-parasitemia-an-open-label-non-comparative-study-in-sub-saharan-africa
#11
Kamija Phiri, Joshua Kimani, George A Mtove, Qinying Zhao, Ricardo Rojo, Jeffery Robbins, Stephan Duparc, Ayman Ayoub, Pol Vandenbroucke
BACKGROUND: Malaria remains one of the most important causes of morbidity and mortality in pregnant women and their newborn babies in sub-Saharan Africa. Intermittent preventive treatment in pregnancy (IPTp) is recommended by the World Health Organization (WHO) to reduce the burden of disease and improve maternal and neonatal survival and general health. Due to the growing resistance to sulfadoxine-pyrimethamine (SP), the current WHO-recommended drug for IPTp, identification of new and effective drugs is an urgent priority...
2016: PloS One
https://www.readbyqxmd.com/read/27858010/bioisosteric-ferrocenyl-containing-quinolines-with-antiplasmodial-and-antitrichomonal-properties
#12
Muneebah Adams, Tameryn Stringer, Carmen de Kock, Peter J Smith, Kirkwood M Land, Nicole Liu, Christina Tam, Luisa W Cheng, Mathew Njoroge, Kelly Chibale, Gregory S Smith
Bioisosteric ferrocenyl-containing quinolines and ferrocenylamines containing organosilanes and their carbon analogues, were prepared and fully characterised. The molecular structures of two ferrocenyl-containing quinolines, determined using single-crystal X-ray diffraction, revealed that the compounds crystallise in a folded conformation. The compounds were screened for their antiplasmodial activity against the chloroquine-sensitive (NF54) and CQ-resistant (Dd2) strains of P. falciparum, as well as for their cytotoxicity against Chinese Hamster Ovarian (CHO) cells...
November 18, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/27832198/evolution-of-fitness-cost-neutral-mutant-pfcrt-conferring-p-falciparum-4-aminoquinoline-drug-resistance-is-accompanied-by-altered-parasite-metabolism-and-digestive-vacuole-physiology
#13
Stanislaw J Gabryszewski, Satish K Dhingra, Jill M Combrinck, Ian A Lewis, Paul S Callaghan, Matthew R Hassett, Amila Siriwardana, Philipp P Henrich, Andrew H Lee, Nina F Gnädig, Lise Musset, Manuel Llinás, Timothy J Egan, Paul D Roepe, David A Fidock
Southeast Asia is an epicenter of multidrug-resistant Plasmodium falciparum strains. Selective pressures on the subcontinent have recurrently produced several allelic variants of parasite drug resistance genes, including the P. falciparum chloroquine resistance transporter (pfcrt). Despite significant reductions in the deployment of the 4-aminoquinoline drug chloroquine (CQ), which selected for the mutant pfcrt alleles that halted CQ efficacy decades ago, the parasite pfcrt locus is continuously evolving. This is highlighted by the presence of a highly mutated allele, Cam734 pfcrt, which has acquired the singular ability to confer parasite CQ resistance without an associated fitness cost...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27829067/molecular-epidemiology-of-p-vivax-in-iran-high-diversity-and-complex-sub-structure-using-neutral-markers-but-no-evidence-of-y976f-mutation-at-pvmdr1
#14
Yaghoob Hamedi, Khojasteh Sharifi-Sarasiabi, Farzaneh Dehghan, Reza Safari, Sheren To, Irene Handayuni, Hidayat Trimarsanto, Ric N Price, Sarah Auburn
BACKGROUND: Malaria remains endemic at low levels in the south-eastern provinces of Iran bordering Afghanistan and Pakistan, with the majority of cases attributable to P. vivax. The national guidelines recommend chloroquine (CQ) as blood-stage treatment for uncomplicated P. vivax, but the large influx of imported cases enhances the risk of introducing CQ resistance (CQR). METHODOLOGY AND PRINCIPAL FINDINGS: The genetic diversity at pvmdr1, a putative modulator of CQR, and across nine putatively neutral short tandem repeat (STR) markers were assessed in P...
2016: PloS One
https://www.readbyqxmd.com/read/27825387/plasmodium-vivax-multidrug-resistance-1-gene-polymorphism-in-french-guiana
#15
Emilie Faway, Lise Musset, Stéphane Pelleau, Béatrice Volney, Jessica Casteras, Valérie Caro, Didier Menard, Sébastien Briolant, Eric Legrand
BACKGROUND: Plasmodium vivax malaria is a major public health problem in French Guiana. Some cases of resistance to chloroquine, the first-line treatment used against P. vivax malaria, have been described in the Brazilian Amazon region. The aim of this study is to investigate a possible dispersion of chloroquine-resistant P. vivax isolates in French Guiana. The genotype, polymorphism and copy number variation, of the P. vivax multidrug resistance gene-1 (pvmdr1) have been previously associated with modification of the susceptibility to chloroquine...
November 8, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27825353/analysis-of-anti-malarial-resistance-markers-in-pfmdr1-and-pfcrt-across-southeast-asia-in-the-tracking-resistance-to-artemisinin-collaboration
#16
Krongkan Srimuang, Olivo Miotto, Pharath Lim, Rick M Fairhurst, Dominic P Kwiatkowski, Charles J Woodrow, Mallika Imwong
BACKGROUND: Declining anti-malarial efficacy of artemisinin-based combination therapy, and reduced Plasmodium falciparum susceptibility to individual anti-malarials are being documented across an expanding area of Southeast Asia (SEA). Genotypic markers complement phenotypic studies in assessing the efficacy of individual anti-malarials. METHODS: The markers pfmdr1 and pfcrt were genotyped in parasite samples obtained in 2011-2014 at 14 TRAC (Tracking Resistance to Artemisinin Collaboration) sites in mainland Southeast Asia using a combination of PCR and next-generation sequencing methods...
November 8, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27823620/immunomodulatory-proteins-fip-gts-and-chloroquine-induce-caspase-independent-cell-death-via-autophagy-for-resensitizing-cisplatin-resistant-urothelial-cancer-cells
#17
I-Lun Hsin, Shao-Chuan Wang, Jian-Ri Li, Tsai-Chun Ciou, Chih-Hsien Wu, Hung-Ming Wu, Jiunn-Liang Ko
BACKGROUND: Chloroquine, a lysosomal inhibitor, is used for malaria, rheumatoid arthritis, and lupus erythematosus therapy. In our previous study, FIP-gts, an immunomodulatory protein from Ganoderma tsugae, inhibited cell viability in lung cancer cells and urothelial cancer cells. Urothelial carcinoma is the most common type of bladder cancer. Cisplatin resistance is an important issue in urothelial carcinoma therapy. PURPOSE: The aim of this study is to investigate the effect of combination treatment with FIP-gts and chloroquine on cytotoxicity to resensitize the cisplatin-resistant cells...
December 1, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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/27815887/measurement-of-salmonella-enterica-internalization-and-vacuole-lysis-in-epithelial-cells
#19
Jessica A Klein, TuShun R Powers, Leigh A Knodler
Establishment of an intracellular niche within mammalian cells is key to the pathogenesis of the gastrointestinal bacterium, Salmonella enterica serovar Typhimurium (S. Typhimurium). Here we will describe how to study the internalization of S. Typhimurium into human epithelial cells using the gentamicin protection assay. The assay takes advantage of the relatively poor penetration of gentamicin into mammalian cells; internalized bacteria are effectively protected from its antibacterial actions. A second assay, the chloroquine (CHQ) resistance assay, can be used to determine the proportion of internalized bacteria that have lysed or damaged their Salmonella-containing vacuole and are therefore residing within the cytosol...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27815736/magnetic-nanoparticles-are-highly-toxic-to-chloroquine-resistant-plasmodium-falciparum-dengue-virus-den-2-and-their-mosquito-vectors
#20
Kadarkarai Murugan, Jiang Wei, Mohamad Saleh Alsalhi, Marcello Nicoletti, Manickam Paulpandi, Christina Mary Samidoss, Devakumar Dinesh, Balamurugan Chandramohan, Chellasamy Paneerselvam, Jayapal Subramaniam, Chithravel Vadivalagan, Hui Wei, Pandiyan Amuthavalli, Anitha Jaganathan, Sandhanasamy Devanesan, Akon Higuchi, Suresh Kumar, Al Thabiani Aziz, Devaraj Nataraj, Baskaralingam Vaseeharan, Angelo Canale, Giovanni Benelli
A main challenge in parasitology is the development of reliable tools to prevent or treat mosquito-borne diseases. We investigated the toxicity of magnetic nanoparticles (MNP) produced by Magnetospirillum gryphiswaldense (strain MSR-1) on chloroquine-resistant (CQ-r) and sensitive (CQ-s) Plasmodium falciparum, dengue virus (DEN-2), and two of their main vectors, Anopheles stephensi and Aedes aegypti, respectively. MNP were studied by Fourier-transform infrared spectroscopy and transmission electron microscopy...
November 4, 2016: Parasitology Research
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