Affiliation:
1. Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso
2. Department of Medicine, University of California, San Francisco, California
Abstract
ABSTRACT
Artemether-lumefantrine (AL), dihydroartemisinin-piperaquine (DP), and amodiaquine-sulfadoxine-pyrimethamine (AQ-SP) offer excellent antimalarial efficacy but may select for parasite polymorphisms that decrease drug sensitivity. We evaluated the selection of known polymorphisms in genes encoding putative transporters (
pfcrt
and
pfmdr1
) and SP targets (
pfdhfr
and
pfdhps
) in parasites that caused new infections within 42 days of therapy for uncomplicated falciparum malaria in Burkina Faso. In 559 children in 2006, 42-day genotype-uncorrected failures were seen in 31.2% with AL, 11.8% with AQ-SP, and 7.6% with DP. After prior AL therapy, selection of wild-type sequences was seen for K76T in
pfcrt
(72.7% mixed or mutant results pretreatment versus 52.1% in new infections;
P
= 0.008) and N86Y (36.0% versus 18.7%;
P
= 0.025) and Y184F (66.7% versus 45.8%;
P
= 0.009) in
pfmdr1
. After prior AQ-SP therapy, selection of mutant sequences was seen for N51I (30.8% versus 61.5%;
P
= 0.05), C59R (28.2% versus 76.9%;
P
= 0.002), and S108N (30.8% versus 76.9%;
P
= 0.005) in
pfdhfr
. After prior DP therapy, selection was not seen for K76T (72.7% versus 77.8%;
P
= 0.96) in
pfcrt
or N86Y (36.0% versus 33.3%;
P
= 0.84), Y184F (66.7% versus 77.8%;
P
= 0.39), or D1246Y (9.3% versus 0%;
P
= 0.42) in
pfmdr1
. In 378 additional treatments with DP in 2007, 42-day uncorrected failure was seen in 10.9%. After prior DP, selection was again not seen for K76T (66.7% mixed or mutant results versus 59.5%;
P
= 0.43) in
pfcrt
or N86Y (38.7% versus 40.5%;
P
= 0.85), Y184F (67.6% versus 73.0%;
P
= 0.54), or D1246Y (3.6% versus 8.1%;
P
= 0.50) in
pfmdr1
. Despite its chemical similarity, piperaquine did not select for the same polymorphisms as chloroquine or AQ, suggesting different mechanisms of resistance.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
85 articles.
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