High prevalence of markers for sulfadoxine and pyrimethamine resistance in Plasmodium falciparum in the absence of drug pressure in the Ashanti region of Ghana.
Markers of Plasmodium falciparum resistance to chloroquine (CQ) and pyrimethamine-sulfadoxine (PYR-SDX) are widespread in areas where malaria is endemic. In an area where the use PYR-SDX is negligible, the Ashanti Region of Ghana, West Africa, adult individuals were enrolled in an analysis of CQ- and PYR-SDX-associated molecular resistance markers in 2001 (n = 177) and 2003 (n = 180). Parasite prevalence, as assessed by PCR assays, were 56.5 and 48.8% in 2001 and 2003, respectively. A high frequency of CQ, PYR, and SDX resistance markers was observed, whereby, as a weak trend, the frequency was higher in 2003. The quintuple combination of three pfdhfr mutations and two pfdhps mutations has previously been recognized to be the most important determinant of PYR-SDX resistance. Approximately 60% of parasite carriers harbored fourfold mutated parasites, indicative of a considerable risk for a switch to high-level PYR-SDX resistance in an area where the rate of PYR-SDX use is low. Among the factors contributing to the high frequency of PYR-SDX resistance-associated mutations are background use of PYR-SDX, past use of PYR for malaria prophylaxis, cross-resistance of trimethoprim with PYR, and the sufficient biological fitness of resistant parasites in the absence of drug pressure.
Marks
Florian
F
Department of Molecular Medicine, Bernhard-Nocht Institute for Tropical Medicine, Bernhard Nocht Str. 74, 20359 Hamburg, Germany.
Evans
Jennifer
J
Meyer
Christian G
CG
Browne
Edmund N
EN
Flessner
Christa
C
von Kalckreuth
Vera
V
Eggelte
Teunis A
TA
Horstmann
Rolf D
RD
May
Jürgen
J
D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D015415:Biomarkers; D002738:Chloroquine / Q000494:pharmacology; D004338:Drug Combinations; D004351:Drug Resistance; D006801:Humans; D010963:Plasmodium falciparum / Q000187:drug effects*; D011739:Pyrimethamine / Q000494:pharmacology*; D013413:Sulfadoxine / Q000494:pharmacology*
D000962:Antimalarials; D015415:Biomarkers; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine
Trop Med Int Health. 2002 May;7(5):395-408
12000649
East Afr Med J. 1954 Feb;31(2):41-6
13151067
FEMS Microbiol Lett. 2002 Oct 8;215(2):249-53
12399042
J Appl Microbiol. 2003;94(2):289-94
12534821
Am J Trop Med Hyg. 2003 Feb;68(2):143-6
12641402
Am J Trop Med Hyg. 2000 Feb;62(2):210-6
10813475
Am J Trop Med Hyg. 2000 Mar;62(3):396-401
11037785
N Engl J Med. 2001 Jan 25;344(4):257-63
11172152
J Infect Dis. 2001 Sep 15;184(6):770-6
11517439
Lancet. 2001 Sep 29;358(9287):1066-7
11589941
J Infect Dis. 2002 Feb 1;185(3):380-8
11807721
Sci Prog. 2002;85(Pt 1):89-111
11969121
Trends Parasitol. 2003 Apr;19(4):158-60; author reply 160-1
12689643
Am J Trop Med Hyg. 2003 May;68(5):586-9
12812351
Trends Parasitol. 2003 Oct;19(10):432-5; discussion 435-6
14519577
Mol Microbiol. 2003 Nov;50(4):1319-27
14622418
Antimicrob Agents Chemother. 2004 Feb;48(2):466-72
14742196
Lancet. 2004 Apr 24;363(9418):1372
15112707
Bull World Health Organ. 1968;38(3):488-91
5302340
Nature. 1969 Aug 9;223(5206):635-6
5799541
Soc Sci Med. 1975 Apr-May;9(4-5):241-8
1154046
J Med Assoc Thai. 1977 Dec;60(12):648-54
342649
Med Parazitol (Mosk). 1984 Jul-Aug;(4):13-6
6384755
Proc Natl Acad Sci U S A. 1988 Dec;85(23):9114-8
2904149
Angew Parasitol. 1988 Nov;29(4):211-3
3072886
Parasitology. 1990 Jun;100 Pt 3:377-81
2362764
Exp Parasitol. 1994 Mar;78(2):194-202
8119374
Am J Trop Med Hyg. 1996 Sep;55(3):350-1
8842128
Am J Trop Med Hyg. 1996 Nov;55(5):467-71
8940973
Trans R Soc Trop Med Hyg. 1996 Sep-Oct;90(5):563-7
8944275
Trans R Soc Trop Med Hyg. 1996 Nov-Dec;90(6):678-80
9015515
Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1124-9
9037017
J Infect Dis. 1997 Dec;176(6):1590-6
9395372
J Clin Invest. 1998 May 1;101(9):2008-16
9576766
Trop Med Int Health. 2002 Jul;7(7):577-83
12100440