title: Confirmed Plasmodium vivax Resistance to Chloroquine in Central Vietnam.
abstract: Plasmodium vivax resistance to chloroquine (CQ) is currently reported in almost all countries where P. vivax is endemic. In Vietnam, despite a first report on P. vivax resistance to chloroquine published in the early 2000s, P. vivax was still considered sensitive to CQ. Between May 2009 and December 2011, a 2-year cohort study was conducted in central Vietnam to assess the recommended radical cure regimen based on a 10-day course of primaquine (0.5 mg/kg/day) together with 3 days of CQ (25 mg/kg). Here we report the results of the first 28-day follow-up estimating the cumulative risk of P. vivax recurrences together with the corresponding CQ blood concentrations, among other endpoints. Out of 260 recruited P. vivax patients, 240 completed treatment and were followed up to day 28 according to the WHO guidelines. Eight patients (3.45%) had a recurrent P. vivax infection, at day 14 (n = 2), day 21 (n = 1), and day 28 (n = 5). Chloroquine blood concentrations, available for 3/8 recurrent infections (days 14, 21, and 28), were above the MIC (>100 ng/ml whole blood) in all of these cases. Fever and parasitemia (both sexual and asexual stages) were cleared by day 3. Anemia was common at day 0 (35.8%), especially in children under 10 years (50%), and hemoglobin (Hb) recovery at day 28 was substantial among anemic patients (median change from day 0 to 28, +1.7 g/dl; interquartile range [IQR], +0.7 to +3.2). This report, based on CQ blood levels measured at the time of recurrences, confirms for the first time P. vivax CQ resistance in central Vietnam and calls for further studies using standardized protocols for accurately monitoring the extent and evolution of P. vivax resistance to chloroquine in Vietnam. These results, together with the mounting evidence of artemisinin resistance in central Vietnam, further highlight the increasing threat of antimalarial drug resistance to malaria elimination in Vietnam.
authors.affiliation: National Institute of Malariology, Parasitology and Entomology, Hanoi, Vietnam phamvinht@gmail.com.
authors.forename: Pham Vinh
authors.initials: PV
authors.lastname: Thanh
authors.affiliation: National Institute of Malariology, Parasitology and Entomology, Hanoi, Vietnam.
authors.forename: Nguyen Van
authors.initials: NV
authors.lastname: Hong
authors.affiliation: Provincial Malaria Station, Tam Ky City, Quang Nam Province, Vietnam.
authors.forename: Nguyen Van
authors.initials: NV
authors.lastname: Van
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
authors.forename: Melva
authors.initials: M
authors.lastname: Louisa
authors.affiliation: Eijkman Oxford Clinical Research Unit, Jakarta, Indonesia.
authors.forename: Kevin
authors.initials: K
authors.lastname: Baird
authors.affiliation: National Institute of Malariology, Parasitology and Entomology, Hanoi, Vietnam.
authors.forename: Nguyen Xuan
authors.initials: NX
authors.lastname: Xa
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Peeters Grietens
authors.affiliation: National Institute of Malariology, Parasitology and Entomology, Hanoi, Vietnam.
authors.forename: Le Xuan
authors.initials: le X
authors.lastname: Hung
authors.affiliation: National Institute of Malariology, Parasitology and Entomology, Hanoi, Vietnam.
authors.forename: Tran Thanh
authors.initials: TT
authors.lastname: Duong
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Anna
authors.initials: A
authors.lastname: Rosanas-Urgell
authors.affiliation: Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Niko
authors.initials: N
authors.lastname: Speybroeck
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium Medical Research Council Unit, Fajara, The Gambia London School of Tropical Medicine & Hygiene, London, United Kingdom.
authors.forename: Umberto
authors.initials: U
authors.lastname: D'Alessandro
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Annette
authors.initials: A
authors.lastname: Erhart
mesh_terms: D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000139:chemically induced; D000962:Antimalarials / Q000009:adverse effects / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000009:adverse effects / Q000494:pharmacology*; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016780:Malaria, Vivax / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D010966:Plasmodium vivax / Q000187:drug effects* / Q000302:isolation & purification; D011319:Primaquine / Q000494:pharmacology; D016896:Treatment Outcome; D014744:Vietnam; D055815:Young Adult
chemical_list: D000962:Antimalarials; D002738:Chloroquine; D011319:Primaquine