Molekulare Surveillance der Medikamentenresistenz bei Plasmodium falciparum: Evaluation der Methodik anhand von Isolaten aus Laos

Levels of drug resistance of Plasmodium falciparum strains against
antimalarials have increased in Laos. In several studies,
chloroquine (CQ) resistance has been associated with point
mutations in the Pfcrt and pfmdr genes, and
sulphadoxine/pyrimethamine (S/P) resistance with point mutations in
the genes of dihydrofolate reductase (DHFR) and dihydropteroate
synthetase (DHPS). We combined a study of these molecular markers
with an in vivo antimalarial drug sensitivity study in Attapeu
province in the south of Lao PDR. We treated 100 patients with
either CQ, S/P or a combination of both. In the CQ group, Pfcrt
mutations showed a very high sensitivity (100%) but a low
specificity (12.5%) to predict resistance. The combination of
mutations in the Pfcrt and pfmdr genes was highly specific and had
a positive predictive value of 100%. Mutations in the DHPS gene
showed a high correlation with the development of resistance. The
prevalence of mutations in the DHFR gene, especially codon 108 Asn,
was predictive with high sensitivity (100%) but low specificity.
Isolates derived from patients treated with a combination of both
drugs showed a high correlation between the mutation in codon 437
of DHPS gene and in vivo-resistance (odds ratio 16.00, CI). The
study provides evidence for the existence of antimalarial drug
resistance in the south of Lao PDR, and offers a molecular method
to predict resistance.