INDUCTION OF DRUG RESISTANCE IN PLASMODIUM FALCIPARUM: AN INTERMITTENT DRUG EXPOSURE METHOD

• Main Authors: M.Nateghpour (Author), S.A.Ward (Author), R.E. Howells (Author)
• Format: Book
• Published: Tehran University of Medical Sciences, 1998-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2251-6085; 2251-6093
• Keywords: Intermittent drug exposure; Halofantrine; Public aspects of medicine; RA1-1270
• Source: Iranian Journal of Public Health, Vol 27, Iss 1-2 (1998)

The production of experimentally induced drug resistance in the laboratory provides valuable opportunities for investigators to study the nature and genetics of drug resistance mechanisms to a given agent, patterns of cross resistance and the mode of action of drugs. At the beginning the continuous drug exposure was chosen as a standard procedure to produce drug- resistant strains of P. falciparum,.but later on some other methods were also applied. An intermittent drug exposure method as a novel procedure has been introduced in this study. Intermittent exposure of chloroquine resistant Kl and chloroquine sensitive T9.96 strains of P. falciparum to halofantrine culminated in a relatively rapid reduction in sensitivity to the drug. The response of halofantrifle - resistnat K1HF and T9.96 strains and parent parasites to halofantrifle, inefloquine, quinine and chloroquine was determined. The results indicated that the effectiveness of halofantrine to K1HF and T9.96HF strains decreased 9 and 3 folds respectively, compared to the parent parasites. Cross -resistance occurred among halofantrine. mefloquine and quinine. Halofantrine resistance was associated with enhanced chloroquine sensitivity in the strain derived from chloroquine - resistant K1 strain, hut not in the strain derived from chloroquine - sensitive T9.96 parasites.