1921
Volume 57, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645
USD

Abstract

Abstract

The antifolate proguanil is commonly used in the prophylaxis and treatment of malaria. A series of point mutations in the dihydrofolate reductase (DHFR) gene has been linked to differential susceptibility of varied clones or isolates to this drug. To survey the efficiency of proguanil prophylaxis in an African endemic region, and to evaluate the level of proguanil resistance in the corresponding parasite population, we performed drug susceptibility assays with isolates from Senegal, Kenya, and Niger. In parallel, we developed a mutation-specific polymerase chain reaction assay that enabled us to characterize mutations in the DHFR gene of the same isolates without in vitro parasite cultivation. We confirm previously available data showing that parasites harboring a point mutation from Ser 108 to Asn present a decrease in susceptibility to cycloguanil (the active metabolite of proguanil), and we show that mutations in codons 51 and 59 appear to modulate the level of resistance to cycloguanil. No mutations in codons 16 and 164 were detected in resistant parasites, in contrast with results from some previous studies.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.1997.57.646
1997-12-01
2017-11-24
Loading full text...

Full text loading...

http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.1997.57.646
Loading

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error