title: Misclassification of drug failure in Plasmodium falciparum clinical trials in southeast Asia.
abstract: Most trials of antimalarials occur in areas in which reinfections are possible. For Plasmodium falciparum, reinfections are distinguished from recrudescences by polymerase chain reaction analysis of 3 polymorphic genes. However, the validity of this approach has never been rigorously tested. We tested for misclassification in 6 patients from clinical trials in Thailand and Cambodia who were classified as being reinfected by the standard polymerase chain reaction protocol. Using heteroduplex tracking assays and direct DNA sequencing, we found that 5 (83%) of 6 patients were misclassified. Misclassification in this manner overestimates the efficacy of antimalarials and delays the recognition of decreasing therapeutic efficacy, thus delaying potential changes in policy.
authors: Division of Infectious Diseases, School of Medicine, Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors: Jonathan J
authors: JJ
authors: Juliano
authors: Frederic
authors: F
authors: Ariey
authors: Rithy
authors: R
authors: Sem
authors: Noppadon
authors: N
authors: Tangpukdee
authors: Srivicha
authors: S
authors: Krudsood
authors: Carol
authors: C
authors: Olson
authors: Sornchai
authors: S
authors: Looareesuwan
authors: William O
authors: WO
authors: Rogers
authors: Chansuda
authors: C
authors: Wongsrichanalai
authors: Steven R
authors: SR
authors: Meshnick
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002160:Cambodia / Q000453:epidemiology; D016054:DNA, Protozoan / Q000235:genetics; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins; D012008:Recurrence; D013785:Thailand / Q000453:epidemiology; D017211:Treatment Failure
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan; D005819:Genetic Markers; D015800:Protozoan Proteins