Therapeutic efficacy of fixed dose artesunate-mefloquine for the treatment of acute, uncomplicated Plasmodium falciparum malaria in Kampong Speu, Cambodia.
BACKGROUND
Cambodia stopped using co-blistered, non-fixed, artesunate-mefloquine (ASMQ) in 2008 when treatment failure rates approximated 20%. Fixed dose combination (FDC) ASMQ is efficacious against acute uncomplicated, drug resistant Plasmodium falciparum malaria in Southeast Asia but has not been tested in Cambodia.


METHODS
A 42-day WHO therapeutic efficacy study (TES) was conducted in 2010 in Oral, Kampong Speu province, south-west Cambodia, in patients with acute uncomplicated P. falciparum. Daily administered FDC ASMQ for three days was dosed by age. Genotyping of isolates at day 0 and day of recrudescence by polymerase chain reaction (PCR) classified post-treatment recurrent falciparum parasitaemia. Ex vivo drug sensitivity testing ([3H] hypoxanthine method) was performed on baseline parasites and reported as the drug concentration inhibiting 50% parasite growth vs no drug (IC₅₀).


RESULTS
Recruited patients numbered 45; five aged <15 years. On day 3, five of 45 [11.1 (3.7-24.05)] % patients were still parasite-positive; one of whom later failed treatment on day 21. There were 5/45 (11.1%) late treatment failures on day 21, 28 and 35; all were PCR diagnosed recrudescent infections. The day 0 MQ IC₅₀s ranged from 11.5-238.9 (median 58.6) nM.


CONCLUSIONS
This TES demonstrated reasonable efficacy in an area of possible reduced artemisinin sensitivity and high MQ IC₅₀s. Efficacy testing of FDC ASMQ should continue in Cambodia and be considered for reintroduction if efficacy returns.
National Centre for Parasitology, Entomology and Malaria Control, #372, Monivong Blvd, Corner St, 322, Phnom Penh, Cambodia. rithealeang@gmail.com.
Rithea
R
Leang
Sakun
S
Ros
Socheat
S
Duong
Visweswaran
V
Navaratnam
Pharath
P
Lim
Frédéric
F
Ariey
Jean-René
JR
Kiechel
Didier
D
Ménard
Walter R J
WR
Taylor
D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage*; D037621:Artemisinins / Q000008:administration & dosage*; D000077332:Artesunate; D002160:Cambodia; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D005260:Female; D005838:Genotype; D006801:Humans; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D015767:Mefloquine / Q000008:administration & dosage*; D008875:Middle Aged; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D012008:Recurrence; D016896:Treatment Outcome; D055815:Young Adult
D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D000077332:Artesunate; D015767:Mefloquine