Rapid increase in resistance of Plasmodium falciparum to chloroquine-Fansidar in Uganda and the potential of amodiaquine-Fansidar as a better alternative.
Combinations of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) [CQSP] as the first line agents in Uganda have replaced CQ monotherapy. The idea of the combination is to delay the development of malaria resistance to either drug when used alone. We compared the clinical, parasitological and molecular findings of two studies with treatment arms of CQSP, amodiaquine (AQ) plus SP (AQSP) both done in 2003 with a study done 1 year earlier (2002) using SP alone. There was a notable decrease in adequate clinical response (ACR) by day 14 from 92.7% with SP to 80% with the combination CQSP, a year later. AQSP combination was found to have the best effect (94.3% ACR). There were no early treatment failures in the AQSP group. However, treatment failures were recorded at 20% on day 14 and 43% on day 28 for CQSP treatment and 5.7% by day 14 and 28.8% by day 28 in the AQSP group. The number of mutations that are associated with SP resistance increased from 2002 to 2003 at all loci monitored, from 83.8 to 100% at codon 108, 58.7 to 76% at codon 59 in the DHFR gene, and from 58.8 to 86% at codon 437 and 33 to 43% at codon 540 in the DHPS gene. We conclude that there has been a rapid development of resistance since the introduction of the new policy guidelines. AQSP was found to be a superior drug combination compared to CQSP and could be used as a low cost alternative at the moment.
Sendagire
Hakim
H
Department of Biochemistry, Makerere University, P.O. Box 7072, Kampala, Uganda.
Kaddumukasa
Mark
M
Ndagire
Dorothy
D
Aguttu
Clare
C
Nassejje
Maureen
M
Pettersson
Madeleine
M
Swedberg
Gote
G
Kironde
Fred
F
D000655:Amodiaquine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D015800:Protozoan Proteins; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000494:pharmacology / Q000627:therapeutic use*; D014454:Uganda
D000962:Antimalarials; D004338:Drug Combinations; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine