Abstract
BackgroundScarce data are available on Plasmodium falciparum anti-malarial drug resistance in Pakistan. The aim of this study was, therefore, to determine the prevalence of P. falciparum resistance associated polymorphisms in field isolates from southern Pakistan.MethodsBlood samples from 244 patients with blood-slide confirmed P. falciparum mono-infections were collected between 2005-2007. Single nucleotide polymorphisms in the P. falciparum chloroquine resistance transporter (pfcrt K76T), multi drug resistance (pfmdr1 N86Y), dihydrofolate reductase (pfdhfr A16V, N51I, C59R, S108N, I164L) and dihydropteroate synthetase (pfdhps A436S, G437A and E540K) genes and pfmdr1 gene copy numbers were determined using PCR based methods.ResultsThe prevalence of pfcrt 76T and pfmdr1 86Y was 93% and 57%, respectively. The prevalence of pfdhfr double mutations 59R + 108N/51R + 108N was 92%. The pfdhfr triple mutation (51I, 59R, 108N) occurred in 3% of samples. The pfdhfr (51I, 59R, 108N) and pfdhps (437G, 540E) quintuple mutation was found in one isolate. Pfdhps 437G was observed in 51% and 540E in 1% of the isolates. One isolate had two pfmdr1 copies and carried the pfmdr1 86Y and pfcrt 76T alleles.ConclusionsThe results indicate high prevalence of in vivo resistance to chloroquine, whereas high grade resistance to sulphadoxine-pyrimethamine does not appear to be widespread among P. falciparum in southern Pakistan.
Highlights
Scarce data are available on Plasmodium falciparum anti-malarial drug resistance in Pakistan
Chloroquine resistance was first reported from Pakistan in 1984 and was followed by several reports confirming it in Punjab, Afghan refugee camps and areas bordering Afghanistan [5,6,7,8]
The high prevalence of the pfdhfr 108N (99%) and 51I + 108N/59R + 108N (92%) in our study indicate that decreased susceptibility to sulphadoxine-pyrimethamine is widespread in Pakistan
Summary
Scarce data are available on Plasmodium falciparum anti-malarial drug resistance in Pakistan. Development and spread of Plasmodium falciparum resistance to anti-malarial drugs represents a major threat to global malaria control. The incidence of malaria has markedly increased during the last decade and the relative frequency of P. falciparum amongst blood-slide positive malaria infections has increased from 45% in 1995 to 68% in 2006 [2,3,4], probably due to increasing resistance to commonly used monotherapies. In agreement with recommendations by the World Health Organization, Pakistan has adopted artemisinin-based combination therapy (ACT) as treatment of choice for uncomplicated P. falciparum malaria with artesunate plus sulphadoxine-pyrimethamine as first-line treatment [9]. The use of this combination is of some concern as resistance to sulphadoxine-pyrimethamine monotherapy has been reported from western Pakistan [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
