title: Recrudescence in artesunate-treated patients with falciparum malaria is dependent on parasite burden not on parasite factors.
abstract: Artemisinin derivatives are first-line antimalarial drugs in Thailand. No firm evidence of clinically relevant artemisinin resistance exists. When used as monotherapy, artesunate has been associated with a high treatment failure (recrudescence) rate, which could be due to low-level artemisinin resistance. To understand the causes of recrudescence, we retrospectively studied a cohort of 104 malaria patients treated with artesunate monotherapy, 32 of whom recrudesced. There was no difference in in vitro artesunate sensitivities between 6 nonrecrudescent isolates and 16 paired admission and recrudescent isolates. Paired admission and recrudescent isolates from 10 patients were genotyped; only 3 had pfmdr1 mutations. Patients with admission parasitemias >10,000 per microl had a 9-fold higher likelihood of recrudescence (adjusted odds ratio) compared with patients with lower parasitemias. This study suggests (1) recrudescence after treatment with artesunate is not the result of inherent parasite resistance, and (2) admission parasitemia may be useful in choosing therapeutic options.
authors.affiliation: Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand. mtwit@mucc.mahidol.ac.th
authors.forename: Wanida
authors.initials: W
authors.lastname: Ittarat
authors.forename: Amy L
authors.initials: AL
authors.lastname: Pickard
authors.forename: Panthip
authors.initials: P
authors.lastname: Rattanasinganchan
authors.forename: Polrat
authors.initials: P
authors.lastname: Wilairatana
authors.forename: Sornchai
authors.initials: S
authors.lastname: Looareesuwan
authors.forename: Kathryn
authors.initials: K
authors.lastname: Emery
authors.forename: Jonathan
authors.initials: J
authors.lastname: Low
authors.forename: Rachanee
authors.initials: R
authors.lastname: Udomsangpetch
authors.forename: Steven R
authors.initials: SR
authors.lastname: Meshnick
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use*; D000077332:Artesunate; D015331:Cohort Studies; D004351:Drug Resistance; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology* / Q000469:parasitology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics*; D012008:Recurrence; D012189:Retrospective Studies; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D013785:Thailand / Q000453:epidemiology
chemical_list: D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D037621:Artemisinins; D015800:Protozoan Proteins; D012717:Sesquiterpenes; C059987:mdr gene protein, Plasmodium; D000077332:Artesunate