Schlüsselwörter
(Englisch)
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Malaria, Plasmodium falciparum, drug resistance, molecular markers, micro arrays, sequence analysis, SNP, field studies, monitoring, genetic resistance index
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Projektziele
(Englisch)
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To assess the usefulness of molecular markers as a public health tool to i) decide on the need for change in treatment policies, ii) monitor the development of resistance to the standard drug regimen and to the new drug introduced, and iii) assess the reversal of resistance of the circulating parasite strains after drug changes, all of that using the newly developed DNA Chip technology.
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Abstract
(Englisch)
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Since drug resistance is encoded in single nucleotide polymorphisms in malaria, we propose to use a newly developed SNP typing method to conduct community surveys in order to obtain data on the genetic profile of the circulating parasite population. Longitudinally obtaining data on all drug resistance associated SNPs will enable us to compare this data with drug efficacy data obtained at the health facilities. Capturing the dynamics of these resistance traits might allow us to predict drug efficacy by only sampling parasites from the community. However, this approach of a genetic resistance index must be validated in different endemic sites and we will conduct our studies in three highly endemic regions of Tanzania, and in three sites in Papua New Guinea being characterized by a different endemicity.
Since in both countries drug policy recently has changed we also might be able to follow increase of resistance against the newly introduced drugs, but, if occurring, we will capture the reversal of rug resistance once the selection pressure is taken away by withdrawal of the drug.
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Publikationen / Ergebnisse
(Englisch)
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Al-Yaman F, Genton B, Mokela D, Alpers MP. Resistance of Plasmodium falciparum in vivo to 3 days' treatment with quinine and single-dose Fansidar. Papua New Guinea Medical Journal 1994;37:54-56.
Al-Yaman F, Genton B, Mokela D, Narara A, Raiko A, Alpers M. Resistance of Plasmodium falciparum to amodiaquine, chloroquine and quinine in the Madang Province of Papua New Guinea, 1990-1993. Papua New Guinea Medical Journal 1996;39:16-22.
Genton B, Lorry K, Wines B, Baea K, Alpers MP. In vivo and in vitro sensitivity of Plasmodium falciparum, vivax and malariae and clinical response after standard treatment in Papua New Guinea. WHO/TDR report M2/181/221, 1997.
Reeder JC, Rieckmann KH, Genton B, Lorry K, Wines B, Cowman AF. Point mutations in the dihydrofolate reductase and dihydropteroate synthetase genes and in vitro susceptibility to pyrimethamine and cycloguanil of Plasmodium falciparum isolates from Papua New Guinea. American Journal of Tropical Medicine and Hygiene 1996;55:209-213.
Al-Yaman F, Genton B, Reeder J, Anders R, Alpers MP. Evidence that recurrent Plasmodium falciparum parasitaemias is caused by recrudescence of resistant parasites. American Journal of Tropical Medicine and Hygiene 1997a;56:436-439.
Felger I, Tavul L, Narara A, Genton B, et al. The use of polymerase chain reaction for more sensitive detection of Plasmodium falciparum. Papua New Guinea Medical Journal 1995;38:52-56.
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