Abstract
BackgroundMalaria 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.MethodsBlood 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.ResultsThe 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).ConclusionThe 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.
Highlights
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
As a consequence of increasing rates of clinical resistance to CQ, the protocol at the Pediatric Hospital David Bernardino (HPDB) was changed, in 2006, two combined therapies artesunate with lumefantrine (Coartem®), and amodiaquine (AQ) with sulphadoxine-pyrimethamine (SP – Fansidar®) as first-line treatments of uncomplicated malaria
Patients and parasites From the 245 isolates of P. falciparum parasites used in this study, 199 samples were successfully typed by PCRRFLP for pfmdr1, for pfcrt 245, for pfdhps 221 and for pfdhfr 224
Summary
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. The pfmdr gene (multidrug resistance) has been described as associated with CQ resistance [5,6,7], with a polymorphism resulting from the substitution of an asparagine for a tyrosine in amino acid 86 (N86Y) in Plasmodium falciparum [8,9,10,11,12,13,14]. CQ resistance is associated with a mutation in the transporter gene pfcrt where the amino acid substitution at pfcrt codon 76 (K to T) has been shown to have a determinant association with the resistance phenotype [15,16,17,18,19]
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