Die Entwicklung eines Malaria-Resistenz-Chips als Mittel zum Management der Malaria Medikamenten-Resistenz

• Forschungsstelle: TPH
• Projektnummer: 1.02
• Projekttitel Englisch: Development of a malaria resistance DNA chip as a public health tool for the management of Plasmodium falciparum malaria drug resistance

Schlüsselwörter (Englisch)

Malaria, Plasmodium falciparum, drug resistance, molecular markers, micro arrays, sequence analysis, SNP, field studies, monitoring, genetic resistance index

Kurzbeschreibung (Englisch)

The main aim is to capture the dynamics of drug resistance against antimalarial drugs in malaria by using a new and innovative tool for the parallel analysis of SNPs. Analysing samples collected during subsequent cross-sectional surveys should allow to establish a resistance factor as indirect measurement for clinical failure of a particular drug and to capture the dynamics over time.

Projektziele (Englisch)

Determination of prevalence of single nucleotide polymorphisms in drug resistance associated genes in naturally infected samples. Longitudinal assessment of drug resistance dynamics.Establishment of predicting model for drug resistance development.

Abstract (Englisch)

Genetic diversity and adaptability of malaria parasites is a major obstacle in the development of rational control strategies against this poverty related disease. Increasing and health threatening drug resistance must be monitored and its development prevented to protect newly introduced anti-malaria drugs. We propose to evaluate a newly developed technique based on DNA micro arrays for monitoring of drug resistance in affected areas. The obtained results will allow to capture the dynamics of drug resistance and to forecast its development by establishing a community based Genetic Resistance Factor, providing a tool for rational and evidence based decisions on optimal use of drugs. We will also investigate the relationship of in vivo drug sensitivity and in vitro susceptibility to a panel of anti-malarials with prevalence of multi-locus SNPs on epidemiological level providing correlates for clinical resistance. Gene sequencing will identify additional informative codons. Newly identified markers will be incorporated into the DNA chip.The analysis will be carried out in several malaria endemic areas world wide.

Publikationen / Ergebnisse (Englisch)

Schneider, A.G., Felger, I., Smith, T., Abdullah, S., Beck, H.P., Mshinda, H. 2001 A point mutation in codon 76 of pfcrt of Plasmodium falciparum is positively selected for by chloroquine treatment in Tanzania. Infection, Genetics, and Evolution 18, 1-7