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Scientific Articles

Transcriptomic Profiling of the Saccharomyces cerevisiae Response to Quinine Reveals a Glucose Limitation Response Attributable to Drug-Induced Inhibition of Glucose Uptake

November 18, 2009 - 12:43 -- Patrick Sampao
Author(s): 
Sandra C. dos Santos, Sandra Tenreiro, Margarida Palma,Jorg Becker, and Isabel Sá-Correia.
Reference: 
Antimicrobial Agents and Chemotherapy, December 2009, p. 5213-5223, Vol. 53, No. 12, doi:10.1128/AAC.00794-09

Quinine has been employed in the treatment of malaria for centuries and is still used against severe Plasmodium falciparum malaria. However, its interactions with the parasite remain poorly understood and subject to debate. In this study, we used the Saccharomyces cerevisiae eukaryotic model to better understand quinine's mode of action and the mechanisms underlying the cell response to the drug.

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Review; Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria

November 18, 2009 - 12:42 -- Kabogo Ndegwa
Author(s): 
Richard T. Eastman1 & David A. Fidock1
Reference: 
Nature Reviews Microbiology 7, 864-874 (December 2009) doi:10.1038/nrmicro2239

Plasmodium falciparum resistance to chloroquine and sulphadoxine–pyrimethamine has led to the recent adoption of artemisinin-based combination therapies (ACTs) as the first line of treatment against malaria. ACTs comprise semisynthetic artemisinin derivatives paired with distinct chemical classes of longer acting drugs. These artemisinins are exceptionally potent against the pathogenic asexual blood stages of Plasmodium parasites and also act on the transmissible sexual stages.

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The dynamics of mutations associated with anti-malarial drug resistance in Plasmodium falciparum.

November 18, 2009 - 12:38 -- Kabogo Ndegwa
Author(s): 
Ananias A. Escalante, David L. Smith, Yuseob Kim.
Reference: 
Trends in Parasitology, Volume 25, Issue 12, December 2009, Pages 557-563, doi:10.1016/j.pt.2009.09.008

The evolution of resistance in Plasmodium falciparum against safe and affordable drugs such as chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) is a major global health threat. Investigating the dynamics of resistance against these antimalarial drugs will lead to approaches for addressing the problem of resistance in malarial parasites that are solidly based in evolutionary genetics and population biology. In this article, we discuss current developments in population biology modeling and evolutionary genetics.

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Redefining the role of de novo fatty acid synthesis in Plasmodium parasites.

November 18, 2009 - 12:36 -- Kabogo Ndegwa
Author(s): 
Alice S. Tarun, Ashley M. Vaughan, Stefan H.I. Kappe.
Reference: 
Trends in Parasitology, Volume 25, Issue 12, December 2009, Pages 545-550, doi:10.1016/j.pt.2009.09.002

Fatty acids are essential components of membranes, and are also involved in cell signalling. Plasmodium, the parasite that causes malaria, scavenges fatty acids from its hosts. However, Plasmodium also possesses enzymes for a prokaryotic-like de novo fatty acid synthesis pathway, which resides in the apicoplast. Recent research has demonstrated that Plasmodium parasites depend on de novo fatty acid synthesis only for liver-stage development.

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Mechanisms of Resistance; Characteristics of Genetic Hitchhiking around Dihydrofolate Reductase Gene Associated with Pyrimethamine Resistance in Plasmodium falciparum Isolates from India .

November 18, 2009 - 12:34 -- Patrick Sampao
Author(s): 
Vanshika Lumb, Manoj K. Das, Neeru Singh, Vas Dev, Wajihullah,4 and Yagya D. Sharma
Reference: 
Antimicrobial Agents and Chemotherapy, December 2009, p. 5173-5180, Vol. 53, No. 12, doi:10.1128/AAC.00045-09

Sulfadoxine-pyrimethamine (SP) resistance in Plasmodium falciparum has been widespread across continents, causing the major hurdle of controlling malaria. Resistance is encoded mainly by point mutations in P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) target genes. To study the origin and evolution of pyrimethamine resistance on the Indian subcontinent, microsatellite markers flanking the pfdhfr gene were mapped. Here we describe the characteristics of genetic hitchhiking around the pfdhfr gene among 190 P. falciparum isolates.

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Malaria vaccines – how and when to proceed?

November 18, 2009 - 12:34 -- Kabogo Ndegwa
Author(s): 
Alister G. Craig, Anthony A. Holder, Odile Y. Leroy, Roland A. Ventura.
Reference: 
Trends in Parasitology, Volume 25, Issue 12, December 2009, Pages 535-537, doi:10.1016/j.pt.2009.09.005

In the field of malaria vaccines, there are many barriers to moving lead candidates from the bench into developmental programmes before clinical testing. Many of the same challenges are to be found in the field of vaccines for other infectious diseases. Here, we briefly outline the process of pre-clinical development to help identify ways to support the translation of laboratory-based information into viable vaccine candidates.

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ABC - antibiotics-based combinations for the treatment of severe malaria?

November 18, 2009 - 12:31 -- Kabogo Ndegwa
Author(s): 
Harald Noedl.
Reference: 
Trends in Parasitology, Volume 25, Issue 12, December 2009, Pages 540-544, doi:10.1016/j.pt.2009.09.001.

Almost one million people die of severe malaria every year. In recent years, artemisinin-based combination therapies have become the backbone of the treatment of uncomplicated falciparum malaria and have helped to reduce the burden of malaria in large parts of the malaria-endemic world. However, the treatment of severe malaria,the clinical syndrome responsible for most malaria-associated deaths, remains largely unaffected by this development.

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Pharmacogenetics of antimalarial drugs: effect on metabolism and transport.

November 18, 2009 - 12:28 -- Kabogo Ndegwa
Author(s): 
Reinhold Kerb, Richard Fux, Klaus Mörike, Peter G Kremsner, José Pedro Gil, Christoph H Gleiter, Matthias Schwab.
Reference: 
The Lancet Infectious Diseases, Volume 9, Issue 12, December 2009, Pages 760-774, doi:10.1016/S1473-3099(09)70320-2.

The prevention and management of malaria is primarily based on the use of drugs. Clinical trials have however revealed that between individuals there is large variability in the pharmacokinetic profiles of many antimalarial drugs. The resulting variations in concentrations of the drug within plasma might lead to either suboptimum effectiveness or drug toxicity in some patients.

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Mechanisms of action; Role of Plasmodium falciparum Digestive Vacuole Plasmepsins in the Specificity and Antimalarial Mode of Action of Cysteine and Aspartic Protease Inhibitors

November 18, 2009 - 12:21 -- Patrick Sampao
Author(s): 
Pedro A. Moura, John B. Dame, and David A. Fidock
Reference: 
Antimicrobial Agents and Chemotherapy, December 2009, p. 4968-4978, Vol. 53, No. 12, doi:10.1128/AAC.00882-09

Hemoglobin (Hb) degradation is essential for the growth of the intraerythrocytic stages of malarial parasites. This process, which occurs inside an acidic digestive vacuole (DV), is thought to involve the action of four aspartic proteases, termed plasmepsins (PMs). These enzymes have received considerable attention as potential antimalarial drug targets.

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Artemether Lumefantrine versus Dihydroartemisinin Piperaquine for Falciparum Malaria: A Longitudinal, Randomized Trial in Young Ugandan Children

November 16, 2009 - 14:04 -- Ingeborg van Schayk
Author(s): 
Emmanuel Arinaitwe, Taylor G. Sandison, Humphrey Wanzira, Abel Kakuru, Jaco Homsy, Julius Kalamya, Moses R. Kamya, Neil Vora, Bryan Greenhouse, Philip J. Rosenthal, Jordan Tappero, and Grant Dorsey
Reference: 
Clinical Infectious Diseases 2009; Volume 49, Number 11: Pages 1629–1637, DOI: 10.1086/647946

Artemisinin-based combination therapies are now widely recommended as first-line treatment for uncomplicated malaria. However, which therapies are optimal is a matter of debate. We aimed to compare the short- and longer-term efficacy of 2 leading therapies in a cohort of young Ugandan children.

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