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Malaria drug resistance

Kritpaphat Tantiamornkul, Tepanata Pumpaibool, Jittima Piriyapongsa, Richard Culleton, Usa Lek-Uthai
The prevalence of Plasmodium vivax is increasing in the border regions of Thailand; one potential problem confounding the control of malaria in these regions is the emergence and spread of drug resistance. The aim of this study was to determine the genetic diversity in genes potentially linked to drug resistance in P. vivax parasites isolated from four different border regions of Thailand; Thai-Myanmar (Tak, Mae Hong Son and Prachuap Khiri Khan Provinces), and Thai-Cambodian borders (Chanthaburi Province). Isolates were collected from 345 P...
April 12, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Manel Ouji, Jean-Michel Augereau, Lucie Paloque, Françoise Benoit-Vical
The use of artemisinin-based combination therapies (ACTs), which combine an artemisinin derivative with a partner drug, in the treatment of uncomplicated malaria has largely been responsible for the significant reduction in malaria-related mortality in tropical and subtropical regions. ACTs have also played a significant role in the 18% decline in the incidence of malaria cases from 2010 to 2016. However, this progress is seriously threatened by the reduced clinical efficacy of artemisinins, which is characterised by delayed parasitic clearance and a high rate of recrudescence, as reported in 2008 in Western Cambodia...
2018: Parasite: Journal de la Société Française de Parasitologie
Pedro Henrique Reis da Silva, Melina Luiza Vieira Diniz, Gerson Antônio Pianetti, Isabela da Costa César, Maria Elisa Scarpelli Ribeiro E Silva, Roberto Fernando de Souza Freitas, Ricardo Geraldo de Sousa, Christian Fernandes
Lumefantrine is the first-choice treatment of Falciparum uncomplicated malaria. Recent findings of resistance to lumefantrine has brought attention for the importance of therapeutic monitoring, since exposure to subtherapeutic doses of antimalarials after administration is a major cause of selection of resistant parasites. Therefore, this study focused on the development of innovative, selective, less expensive and stable molecularly imprinted polymers (MIPs) for solid-phase extraction (SPE) of lumefantrine from human plasma to be used in drug monitoring...
July 1, 2018: Talanta
Maureen A Carey, Vincent Covelli, Audrey Brown, Gregory L Medlock, Mareike Haaren, Jessica G Cooper, Jason A Papin, Jennifer L Guler
Metabolomics is increasingly popular for the study of pathogens. For the malaria parasite Plasmodium falciparum , both targeted and untargeted metabolomics have improved our understanding of pathogenesis, host-parasite interactions, and antimalarial drug treatment and resistance. However, purification and analysis procedures for performing metabolomics on intracellular pathogens have not been explored. Here, we purified in vitro -grown ring-stage intraerythrocytic P. falciparum parasites for untargeted metabolomics studies; the small size of this developmental stage amplifies the challenges associated with metabolomics studies as the ratio between host and parasite biomass is maximized...
April 25, 2018: MSphere
Andrew Bradley Nuss, Mark R Brown, Upadhyayula Suryanarayana Murty, Monika Gulia-Nuss
Lymphatic filariasis, commonly known as elephantiasis, is a painful and profoundly disfiguring disease. Wuchreria bancrofti (Wb) is responsible for >90% of infections and the remainder are caused by Brugia spp. Mosquitoes of the genera Culex (in urban and semi-urban areas), Anopheles (in rural areas of Africa and elsewhere), and Aedes (in Pacific islands) are the major vectors of W. bancrofti. A preventive chemotherapy called mass drug administration (MDA), including albendazole with ivermectin or diethylcarbamazine citrate (DEC) is used in endemic areas...
April 12, 2018: PLoS Neglected Tropical Diseases
Sarah-Blythe Ballard, Allison Salinger, Paul M Arguin, Meghna Desai, Kathrine R Tan
Malaria infection during pregnancy is associated with an increased risk for maternal and fetal complications. In the United States, treatment options for uncomplicated, chloroquine-resistant Plasmodium falciparum and P. vivax malaria in pregnant women are limited to mefloquine or quinine plus clindamycin (1). However, limited availability of quinine and increasing resistance to mefloquine restrict these options. Strong evidence now demonstrates that artemether-lumefantrine (AL) (Coartem) is effective and safe in the treatment of malaria in pregnancy...
April 13, 2018: MMWR. Morbidity and Mortality Weekly Report
Yasaman KalantarMotamedi, Richard T Eastman, Rajarshi Guha, Andreas Bender
BACKGROUND: Nearly half of the world's population (3.2 billion people) were at risk of malaria in 2015, and resistance to current therapies is a major concern. While the standard of care includes drug combinations, there is a pressing need to identify new combinations that can bypass current resistance mechanisms. In the work presented here, a combined transcriptional drug repositioning/discovery and machine learning approach is proposed. METHODS: The integrated approach utilizes gene expression data from patient-derived samples, in combination with large-scale anti-malarial combination screening data, to predict synergistic compound combinations for three Plasmodium falciparum strains (3D7, DD2 and HB3)...
April 11, 2018: Malaria Journal
Lisa Gruber, Sara Abdelfatah, Tony Fröhlich, Christoph Reiter, Volker Klein, Svetlana B Tsogoeva, Thomas Efferth
Two major obstacles for successful cancer treatment are the toxicity of cytostatics and the development of drug resistance in cancer cells during chemotherapy. Acquired or intrinsic drug resistance is responsible for almost 90% of treatment failure. For this reason, there is an urgent need for new anticancer drugs with improved efficacy against cancer cells, and with less toxicity on normal cells. There are impressive examples demonstrating the success of natural plant compounds to fight cancer, such as Vinca alkaloids, taxanes, and anthracyclines...
April 6, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Raj Badhan, Zaril Zakaria, Olusola Olafuyi
Ivermectin has demonstrated many successes in the treatment of a range of nematode infections. Considering the increase in malaria resistance attention has turned towards ivermectin as a candidate for repurposing for malaria. This study developed and validated an ivermectin physiologically-based pharmacokinetic model in healthy adults (20-50 years) and paediatric (3-5 years/15-25 kg) subjects and in a representative adult malaria population group (Thailand). Dosing optimisation demonstrated a twice daily for 3- or 5-day regimens would provide a time above the LC50 of more than 7 days for adult and paediatric...
April 4, 2018: Journal of Pharmaceutical Sciences
Dennis J Milanowski, Naoya Oku, Laura K Cartner, Heidi R Bokesch, R Thomas Williamson, Josep Saurí, Yizhou Liu, Kirill A Blinov, Yuanqing Ding, Xing-Cong Li, Daneel Ferreira, Larry A Walker, Shabana Khan, Michael T Davies-Coleman, James A Kelley, James B McMahon, Gary E Martin, Kirk R Gustafson
Ambiguities and errors in the structural assignment of organic molecules hinder both drug discovery and total synthesis efforts. Newly described NMR experimental approaches can provide valuable structural details and a complementary means of structure verification. The caulamidines are trihalogenated alkaloids from a marine bryozoan with an unprecedented structural scaffold. Their unique carbon and nitrogen framework was deduced by conventional NMR methods supplemented by new experiments that define 2-bond heteronuclear connectivities, reveal very long-range connectivity data, or visualize the35,37 Cl isotopic effect on chlorinated carbons...
January 14, 2018: Chemical Science
Cedric D J Mbouna, Rufin M T Kouipou, Rodrigue Keumoe, Lauve R Y Tchokouaha, Patrick V T Fokou, Brice M T Tali, Dinkar Sahal, Fabrice F Boyom
BACKGROUND: The emergence and spread of malaria parasites resistant to artemisinin-based combination therapy stresses the need for novel drugs against malaria. Investigating plants used in traditional medicine to treat malaria remains a credible option for new anti-malarial drug development. This study was aimed at investigating the antiplasmodial activity and selectivity of extracts and fractions from Terminalia mantaly and Terminalia superba (Combretaceae) that are used in Cameroon to treat malaria...
April 3, 2018: Malaria Journal
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
Joseph O Muga, Jeremiah W Gathirwa, Matshawandile Tukulula, Walter G Z O Jura
BACKGROUND: Use of chloroquine, an otherwise safe and relatively affordable anti-malarial drug, was discontinued due to widespread prevalence of resistant parasites. Many entrant anti-malarial drugs for treatment of chloroquine resistant malaria raises the concerns of cost and safety among other challenges. Innovative ways of circumventing chloroquine resistance is of paramount importance. Such may include nanoparticulate delivery strategies and targeting. This study evaluated physicochemical properties and in vitro antiplasmodial activity of chloroquine encapsulated heparin functionalized solid lipid nanoparticles (CQ-Hep-SLNs) and non-heparin functionalized SLNs (CQ-SLN) against Plasmodium falciparum...
April 2, 2018: Malaria Journal
Ana L A Godinho, Inês L Martins, João Nunes, Catarina Charneira, Jorge Grilo, Diogo M Silva, Sofia A Pereira, Karina Soto, M Conceição Oliveira, M Matilde Marques, Cristina C Jacob, Alexandra M M Antunes
Drug bioactivation to reactive metabolites capable of covalent adduct formation with bionucleophiles is a major cause of drug-induced adverse reactions. Therefore, elucidation of reactive metabolites is essential to unravel the toxicity mechanisms induced by drugs and thereby identify patient subgroups at higher risk. Etravirine (ETR) was the first second-generation Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) to be approved, as a therapeutic option for HIV-infected patients who developed resistance to the first-generation NNRTIs...
March 25, 2018: European Journal of Pharmaceutical Sciences
Jose Maria Bueno, Felix Calderon, Jesús Chicharro, Juan Carlos de la Rosa, Beatriz Diaz, Jorge Fernandez, Jose M Fiandor, María Teresa Fraile, Mercedes Garcia, Esperanza Herreros, Adolfo García-Pérez, Milagros Lorenzo, Araceli Mallo, Margarita Puente, Anas Saadeddin, Santiago Ferrer, Iñigo Angulo-Barturen, Jeremy N Burrows, María Luisa Leon
Malaria is still one of the most prevalent parasitic infection in the world with half of the world's population at risk of malaria. The effectiveness of current antimalarial therapy is under continuous threat through the spread of resistant Plasmodium strains, even to the most recent class of antimalarial drugs (ACT: artemisinin-combination-therapies). As a consequence, there is still an urgent requirement for new antimalarial drugs. We previously reported the identification of 4(1H)-pyridones as a novel series with potent antimalarial activity...
March 28, 2018: Journal of Medicinal Chemistry
Katia D Ambrosio, Claudiu T Supuran, Giuseppina De Simone
Protozoans belonging to Plasmodium, Leishmania and Trypanosoma genera provoke widespread parasitic diseases with few treatment options and many of the clinically used drugs experiencing an extensive drug resistance phenomenon. In the last several years, the metalloenzyme carbonic anhydrase (CA, EC was cloned and characterized in the genome of these protozoa, with the aim to search for a new drug target for fighting malaria, leishmaniasis and Chagas disease. P. falciparum encodes for a CA (PfCA) belonging to a novel genetic family, the -CA class, L...
March 26, 2018: Current Medicinal Chemistry
Juan Ricardo Cubides, Paola Andrea Camargo-Ayala, Carlos Hernando Niño, Diego Garzón-Ospina, Anggie Ortega-Ortegón, Estefany Ospina-Cantillo, María Fernanda Orduz-Durán, Manuel Elkin Patarroyo, Manuel Alfonso Patarroyo
BACKGROUND: Malaria continues being a public health problem worldwide. Plasmodium vivax is the species causing the largest number of cases of malaria in Asia and South America. Due to the lack of a completely effective anti-malarial vaccine, controlling this disease has been based on transmission vector management, rapid diagnosis and suitable treatment. However, parasite resistance to anti-malarial drugs has become a major yet-to-be-overcome challenge. This study was thus aimed at determining pvmdr1, pvdhfr, pvdhps and pvcrt-o gene mutations and haplotypes from field samples obtained from an endemic area in the Colombian Amazonian region...
March 27, 2018: Malaria Journal
Hoang D Lu, Kurt D Ristroph, Ellen L K Dobrijevic, Jie Feng, Simon A McManus, Yingyue Zhang, William D Mulhearn, Hanu Ramachandruni, Anil Patel, Robert K Prud'homme
Malaria poses a major burden on human health and is becoming increasingly difficult to treat due to the development of microbial resistance to antibiotics, and the resistance issue is exacerbated by a lack of patient adherence to long-term dosing regimens. This situation motivates the development of new antimalarial treatments that are less susceptible to the development of resistance. Developed by Medicines for Malaria Venture (MMV), one promising candidate for malaria treatment is OZ439, which has demonstrated both safety and efficacy in human trials...
March 26, 2018: ACS Infectious Diseases
Aman Kashyap, Rupinder Kaur, Ashish Baldi, Upendra Kumar Jain, Ramesh Chandra, Jitender Madan
Chloroquine diphosphate (CHQ) is primarily used for the treatment of Plasmodium falciparum malaria at the dose of 500 mg orally or 10 mg/kg parenterally. However, point mutations in Plasmodiumfalciparum chloroquine resistance transporter (PfCRT) protein and Plasmodium falciparum multidrug resistance protein 1 (Pfmdr1) localized in digestive vacuole membrane, are responsible for CHQ resistance. Therefore, in present investigation, dextran nanoparticles bearing chloroquine diphosphate (CHQ-DEX-NPs) were formulated by solvent diffusion method of size below 70 nm with zeta-potential of -20...
March 20, 2018: International Journal of Biological Macromolecules
Joana Couto, Miray Tonk, Joana Ferrolho, Sandra Antunes, Andreas Vilcinskas, José de la Fuente, Ana Domingos, Alejandro Cabezas-Cruz
Malaria is a mosquito-borne disease affecting millions of people mainly in Sub-Saharan Africa, Asia and some South American countries. Drug resistance to first-line antimalarial drugs (e.g. chloroquine, sulfadoxine-pyrimethamine and artemisinin) is a major constrain in malaria control. Antimicrobial peptides (AMPs) have shown promising results in controlling Plasmodium spp. parasitemia in in vitro and in vivo models of infection. Defensins are AMPs that act primarily by disrupting the integrity of cell membranes of invasive microbes...
March 15, 2018: Ticks and Tick-borne Diseases
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