The use of genotyping in antimalarial clinical trials: a systematic review of published studies from 1995-2005.
BACKGROUND
The use of genotyping to distinguish recrudescent from new infections is currently recommended for all clinical antimalarial efficacy trials by the World Health Organization. However, genotyping-adjusted drug efficacy estimates may vary between trials due to the use of different genotyping methods and to the different settings in which these methods are applied.


METHODS
A systematic review of all clinical antimalarial efficacy trials published from 1995-2005 was performed to characterize the use of genotyping, including the methods used and the effect of these methods on estimates of drug efficacy.


RESULTS
In a multivariate analysis, the method of interpretation of genotyping results, the studied therapy, the location of the trial, and the duration of study follow-up all had statistically significant effects on the percent of genotyped outcomes classified as new infections.


CONCLUSIONS
Criteria for defining appropriate, standardized genotyping methods for use in different settings are needed to enable more accurate estimates of antimalarial drug efficacy and better comparison between trials. The advantages and disadvantages of different genotyping methods and their potential impact in various settings are discussed.
Collins
William J
WJ
Department of Medicine, University of California, San Francisco, Box 0811, CA 94143, USA. william.collins@ucsf.edu <william.collins@ucsf.edu>
Greenhouse
Bryan
B
Rosenthal
Philip J
PJ
Dorsey
Grant
G
D000349:Africa; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D016054:DNA, Protozoan / Q000235:genetics; D004351:Drug Resistance; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology*; D015999:Multivariate Analysis; D010963:Plasmodium falciparum / Q000235:genetics*
D000962:Antimalarials; D016054:DNA, Protozoan