Prevalence of pfmdr1, pfcrt, pfdhfr and pfdhps mutations associated with drug resistance, in Luanda, Angola.
BACKGROUND
Malaria is the infectious disease causing the highest morbidity and mortality in Angola and due to widespread chloroquine (CQ) resistance, the country has recently changed its first-line treatment recommendations for uncomplicated malaria, from CQ to artemisinin combination therapies (ACT) in adults, and sulphadoxine/pyrimethamine (S/P) in pregnant women. Loss of SP sensitivity is, however, progressing rapidly in Africa and, in this study, were investigated a number of molecular markers associated to CQ and S/P.


METHODS
Blood samples were collected from 245 children with uncomplicated malaria, admitted at the Pediatric Hospital Dr. David Bernardino (HPDB), Angola, and the occurrence of mutations in Plasmodium falciparum was investigated in the pfmdr1 (N86Y) and pfcrt (K76T) genes, associated with CQ resistance, as well as in pfdhfr (C59R) and pfdhps (K540E), conferring SP resistance.


RESULTS
The frequencies of pfmdr1 mutations in codon 86 were 28.6% N, 61.3% Y and 10.1% mixed infections (NY). The frequency of pfcrt mutations in codon 76 were 93.9% K, 5.7% T and 0.4% mixed infections (KT). For pfdhfr the results were in codon 59, 60.6% C, 20.6% R and 18.8% mixed infections (CR). Concerning pfdhps, 6.3% of the isolates were bearers of the mutation 540E and 5.4% mixed infections (K540E).


CONCLUSIONS
The results of this epidemiologic study showed high presence of CQ resistance markers while for SP a much lower prevalence was detected for the markers under study.
Figueiredo
Paula
P
UEI Malária/Centro de Malária e Doenças Tropicais/IHMT/Universidade Nova de Lisboa, Lisbon, Portugal. paulafigueiredo@ihmt.unl.pt
Benchimol
Carla
C
Lopes
Dinora
D
Bernardino
Luís
L
do Rosário
Virgílio E
VE
Varandas
Luís
L
Nogueira
Fátima
F
D000293:Adolescent; D000810:Angola / Q000453:epidemiology; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology; D004094:Dihydropteroate Synthase / Q000235:genetics*; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000453:epidemiology*; D026901:Membrane Transport Proteins / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics*; D011739:Pyrimethamine / Q000494:pharmacology; D013413:Sulfadoxine / Q000494:pharmacology; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
D000962:Antimalarials; D002738:Chloroquine; D004094:Dihydropteroate Synthase; D004338:Drug Combinations; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; D011739:Pyrimethamine; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum; C001205:fanasil, pyrimethamine drug combination