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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Simple and sensitive antimalarial drug screening in vitro and in vivo using transgenic luciferase expressing Plasmodium berghei parasites
International Journal for Parasitology, Volume 38, No. 14, Year 2008
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Description
We report two improved assays for in vitro and in vivo screening of chemicals with potential anti-malarial activity against the blood stages of the rodent malaria parasite Plasmodium berghei. These assays are based on the determination of luciferase activity (luminescence) in small blood samples containing transgenic blood stage parasites that express luciferase under the control of a promoter that is either schizont-specific (ama-1) or constitutive (eef1αa). Assay 1, the in vitro drug luminescence (ITDL) assay, measured the success of schizont maturation in the presence of candidate drugs quantifying luciferase activity in mature schizonts only (ama-1 promoter). The ITDL assay generated drug-inhibition curves and EC50 values comparable to those obtained with standard in vitro drug-susceptibility assays. The second assay, the in vivo drug-luminescence (IVDL) assay, measured parasite growth in vivo in a standard 4-day suppressive drug test, monitored by measuring the constitutive luciferase activity of circulating parasites (eef1αa promoter). The IVDL assay generates growth-curves that are identical to those obtained by manual counting of parasites in Giemsa-stained smears. The reading of luminescence assays is rapid, requires a minimal number of handling steps and no experience with parasite morphology or handling fluorescence-activated cell sorters, produces no radioactive waste and test-plates can be stored for prolonged periods before processing. Both tests are suitable for use in larger-scale in vitro and in vivo screening of drugs. The standard methodology of anti-malarial drug screening and validation, which includes testing in rodent models of malaria, can be improved by the incorporation of such assays. © 2008 Australian Society for Parasitology Inc.
Authors & Co-Authors
Franke-Fayard, Blandine M.D.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Djokovic, D.
Portugal, Oeiras
Instituto Gulbenkian de Ciência
Dooren, M. W.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Ramesar, Jai
Netherlands, Leiden
Leids Universitair Medisch Centrum
Waters, Andrew P.
United Kingdom, Glasgow
Wellcome Trust Centre for Molecular Parasitology
Falade, Mofolusho O.
Nigeria, Ibadan
College of Medicine, University of Ibadan
Kranendonk, Michel
Portugal, Lisbon
Universidade Nova de Lisboa
Martinelli, Axel
Portugal, Lisbon
Instituto de Higiene e Medicina Tropical
Cravo, Pedro Vítor Lemos
Portugal, Lisbon
Instituto de Higiene e Medicina Tropical
Janse, Chris J.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Statistics
Citations: 75
Authors: 10
Affiliations: 6
Identifiers
Doi:
10.1016/j.ijpara.2008.05.012
ISSN:
00207519
Research Areas
Infectious Diseases