Molecular surveillance of drug resistance through imported isolates of Plasmodium falciparum in Europe.
BACKGROUND
Results from numerous studies point convincingly to correlations between mutations at selected genes and phenotypic resistance to antimalarials in Plasmodium falciparum isolates. In order to move molecular assays for point mutations on resistance-related genes into the realm of applied tools for surveillance, we investigated a selection of P. falciparum isolates that were imported during the year 2001 into Europe to study the prevalence of resistance-associated point mutations at relevant codons. In particular, we tested for parasites which were developing resistance to antifolates and chloroquine. The screening results were used to map the prevalence of mutations and, thus, levels of potential drug resistance in endemic areas world-wide.


RESULTS
337 isolates have been tested so far. Prevalence of mutations that are associated with resistance to chloroquine on the pfcrt and pfmdr genes of P. falciparum was demonstrated at high levels. However, the prevalence of mutations associated with resistance to antifolates at the DHFR and DHPS genes was unexpectedly low, rarely exceeding 60% in endemic areas.


CONCLUSIONS
Constant screening of imported isolates will enable TropNetEurop to establish a screening tool for emerging resistance in endemic areas.
Jelinek
Tomas
T
Department of Infectious Diseases and Tropical Medicine, University of Munich, Leopoldstr, 5, 80802 Munich, Germany. jelinek@lrz.uni-muenchen.de
Peyerl-Hoffmann
Gabriele
G
Mühlberger
Nikolai
N
Wichmann
Ole
O
Wilhelm
Michael
M
Schmider
Nadja
N
Grobusch
Martin P
MP
von Sonnenburg
Frank
F
Gascon
Joaquim
J
Laferl
Hermann
H
Hatz
Christoph
C
Alifrangis
Michael
M
Burchard
Gerd
G
McWhinney
Paul
P
Schulze
Marco
M
Kollaritsch
Herwig
H
da Cunha
Saraiva
S
Beran
Jiri
J
Kern
Peter
P
Gjørup
Ida
I
Cuadros
Juan
J
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D003062:Codon; D004094:Dihydropteroate Synthase / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics*; D018432:Drug Resistance, Multiple / Q000235:genetics; D005060:Europe; D005493:Folic Acid Antagonists / Q000494:pharmacology; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D017354:Point Mutation; D015800:Protozoan Proteins / Q000235:genetics*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D014195:Travel
D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D003062:Codon; D005493:Folic Acid Antagonists; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; D002738:Chloroquine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase