Parasitic Sensitivity Tests

Publication Title: 
Journal of Clinical Microbiology

The shelf lives of preserved antimalarial agent-predosed plates according to the type of wrapping and the temperature of storage were studied by measuring the 50% inhibitory concentrations of drug for Plasmodium falciparum 3D7. The shelf life of mefloquine was 8 weeks at 25 degrees C; and those of artesunate, artemisinin, and dihydroartemisinin were a minimum of 24, 12, and 8 weeks, respectively, at 4 degrees C.

Author(s): 
Houzé, Sandrine
Munier, Aline
Paoletti, Xavier
Kaddouri, Halima
Ringwald, Pascal
Le Bras, Jacques
Publication Title: 
Antimicrobial Agents and Chemotherapy

Using nonperoxidic analogs of artemisinin and OZ277 (RBx11160), the strong in vitro antiplasmodial activities of the latter two compounds were shown to be peroxide bond dependent. In contrast, the weak activities of artemisinin and OZ277 against six other protozoan parasites were peroxide bond independent. These data support the iron-dependent artemisinin alkylation hypothesis.

Author(s): 
Kaiser, Marcel
Wittlin, Sergio
Nehrbass-Stuedli, Angela
Dong, Yuxiang
Wang, Xiaofang
Hemphill, Andrew
Matile, Hugues
Brun, Reto
Vennerstrom, Jonathan L.
Publication Title: 
Molecular Microbiology

Artemisinin- and artesunate-resistant Plasmodium chabaudi mutants, AS-ART and AS-ATN, were previously selected from chloroquine-resistant clones AS-30CQ and AS-15CQ respectively. Now, a genetic cross between AS-ART and the artemisinin-sensitive clone AJ has been analysed by Linkage Group Selection. A genetic linkage group on chromosome 2 was selected under artemisinin treatment. Within this locus, we identified two different mutations in a gene encoding a deubiquitinating enzyme.

Author(s): 
Hunt, Paul
Afonso, Ana
Creasey, Alison
Culleton, Richard
Sidhu, Amar Bir Singh
Logan, John
Valderramos, Stephanie G.
McNae, Iain
Cheesman, Sandra
do Rosário, Virgílio
Carter, Richard
Fidock, David A.
Cravo, Pedro
Publication Title: 
Malaria Journal

Molecular markers for drug resistant malaria represent public health tools of great but mostly unrealized potential value. A key reason for the failure of molecular resistance markers to live up to their potential is that data on the their prevalence is scattered in disparate databases with no linkage to the clinical, in vitro and pharmacokinetic data that are needed to relate the genetic data to relevant phenotypes.

Author(s): 
Plowe, Christopher V.
Roper, Cally
Barnwell, John W.
Happi, Christian T.
Joshi, Hema H.
Mbacham, Wilfred
Meshnick, Steven R.
Mugittu, Kefas
Naidoo, Inbarani
Price, Ric N.
Shafer, Robert W.
Sibley, Carol H.
Sutherland, Colin J.
Zimmerman, Peter A.
Rosenthal, Philip J.
Publication Title: 
Antimicrobial Agents and Chemotherapy

Artermisinin and its derivatives are now the mainstays of antimalarial treatment; however, their mechanism of action is only poorly understood. We report on the synthesis of a novel series of epoxy-endoperoxides that can be prepared in high yields from simple starting materials. Endoperoxides that are disubstituted with alkyl or benzyl side chains show efficient inhibition of the growth of both chloroquine-sensitive and -resistant strains of Plasmodium falciparum.

Author(s): 
del Pilar Crespo, Maria
Avery, Thomas D.
Hanssen, Eric
Fox, Emma
Robinson, Tony V.
Valente, Peter
Taylor, Dennis K.
Tilley, Leann
Publication Title: 
Malaria Journal

BACKGROUND: The emergence of Plasmodium falciparum resistant to most currently used antimalarial drugs is the major problem in malaria control along the Thai-Myanmar and Thai-Cambodia borders. Although artemisinin-based combination therapy has been recommended for the treatment of multidrug-resistant falciparum malaria, these combinations are not available for some people, such as travelers from North America.

Author(s): 
Khositnithikul, Rommanee
Tan-Ariya, Peerapan
Mungthin, Mathirut
Publication Title: 
Antimicrobial Agents and Chemotherapy

The reaction of spiro- and dispiro-1,2,4-trioxolane antimalarials with heme has been investigated to provide further insight into the mechanism of action for this important class of antimalarials. A series of trioxolanes with various antimalarial potencies was found to be unreactive in the presence of Fe(III) hemin, but all were rapidly degraded by reduced Fe(II) heme. The major reaction product from the heme-mediated degradation of biologically active trioxolanes was an alkylated heme adduct resulting from addition of a radical intermediate.

Author(s): 
Creek, Darren J.
Charman, William N.
Chiu, Francis C. K.
Prankerd, Richard J.
Dong, Yuxiang
Vennerstrom, Jonathan L.
Charman, Susan A.
Publication Title: 
Bulletin of the World Health Organization

OBJECTIVE: To evaluate the relative cost-effectiveness in different sub-Saharan African settings of presumptive treatment, field-standard microscopy and rapid diagnostic tests (RDTs) to diagnose malaria. METHODS: We used a decision tree model and probabilistic sensitivity analysis applied to outpatients presenting at rural health facilities with suspected malaria. Costs and effects encompassed those for both patients positive on RDT (assuming artemisinin-based combination therapy) and febrile patients negative on RDT (assuming antibiotic treatment).

Author(s): 
Shillcutt, Samuel
Morel, Chantal
Goodman, Catherine
Coleman, Paul
Bell, David
Whitty, Christopher J. M.
Mills, A.
Publication Title: 
Tropical medicine & international health: TM & IH

OBJECTIVE: To evaluate the in vitro efficacy of artesunate (ATN) and artemether (ATH) against Plasmodium falciparum isolates from the Brazilian Amazon state of Pará and to search for mutations and/or altered copy numbers in the putative resistance-associated pfcrt, pfmdr1 and pfATPase6 genes. METHODS: In vitro efficacy of ATN and ATH was successfully measured in 56 freshly collected P. falciparum isolates, using a conventional WHO microtest with minor modifications. Single nucleotide polymorphisms (SNPs) in the same isolates were inspected using DNA sequencing and/or PCR-RFLP.

Author(s): 
Ferreira, Isabel D.
Martinelli, Axel
Rodrigues, Louise A.
do Carmo, Ediclei L.
do Rosario, Virgilio E.
Póvoa, Marinete M.
Cravo, Pedro
Publication Title: 
PloS One

The objective of this study was to determine the appropriate dose of artesunate for use in a fixed dose combination therapy with chlorproguanil-dapsone (CPG-DDS) for the treatment of uncomplicated falciparum malaria. METHODS: Open-label clinical trial comparing CPG-DDS alone or with artesunate 4, 2, or 1 mg/kg at medical centers in Blantyre, Malawi and Farafenni, The Gambia. The trial was conducted between June 2002 and February 2005, including 116 adults (median age 27 years) and 107 children (median age 38 months) with acute uncomplicated Plasmodium falciparum malaria.

Author(s): 
Wootton, Daniel G.
Opara, Hyginus
Biagini, Giancarlo A.
Kanjala, Maxwell K.
Duparc, Stephan
Kirby, Paula L.
Woessner, Mary
Neate, Colin
Nyirenda, Maggie
Blencowe, Hannah
Dube-Mbeye, Queen
Kanyok, Thomas
Ward, Stephen
Molyneux, Malcolm
Dunyo, Sam
Winstanley, Peter A.

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