Pfmdr1 copy number and arteminisin derivatives combination therapy failure in falciparum malaria in Cambodia

Lim, Pharath; Alker, Alisa P.; Khim, Nimol; Shah, Naman K.; Incardona, Sandra; Socheat, Doung; Yi, Poravuth; Bouth, Denis Mey; Bouchier, Christiane; Puijalon, Odile; Meshnick, Steven R.; Wongsrichanalai, Chansuda; Fandeur, Thierry; Bras, J. Le; Ringwald, Pascal; Ariey, Frédéric

doi:10.1186/1475-2875-8-11

Cited by 152 publications

(118 citation statements)

References 19 publications

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“…23 Similar findings of a reduced sensitivity to lumefantrine in vitro were described by Lim and others, 24 however, in that study the correlation could not be confirmed in vivo . Recently, it has been shown that pfmdr1 gene amplifications were absent from different study sites in PNG, including an area adjacent to our study site.…”

Section: Discussionsupporting

confidence: 71%

Treatment with Coartem (Artemether-Lumefantrine) in Papua New Guinea

Schoepflin

Lin

Kiniboro

et al. 2010

The American Society of Tropical Medicine and Hygiene

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Abstract. A recent drug efficacy trial reported Coartem (artemether-lumefantrine) to be highly effective against Plasmodium falciparum in children less than 5 years of age in Papua New Guinea (PNG). In contrast, we have observed high levels of treatment failures in non-trial conditions in a longitudinal cohort study in the same age group in PNG. Recrudescences were confirmed by genotyping of three different marker genes to provide optimal discrimination power between parasite clones. After excluding genetic host factors by genotyping potentially relevant cytochrome P450 loci, the high number of treatment failures in our study is best explained by poor adherence to complex dosing regimens in combination with insufficient fat supplementation, which are both crucial parameters for the outcome of Coartem treatment. In contrast to the situation in classic drug trials with ideal treatment conditions, our field survey highlights potential problems with unsupervised usage of Coartem in routine clinical practice and under program conditions.

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Section: Discussionsupporting

confidence: 71%

Treatment with Coartem (Artemether-Lumefantrine) in Papua New Guinea

Schoepflin

Lin

Kiniboro

et al. 2010

The American Society of Tropical Medicine and Hygiene

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“…These differences may be related to different sampling times, different pharmacokinetic models, population variations in drug handling, and regional differences in susceptibilities in P. falciparum isolates to artemisinins and the partner drugs 36 in a region where recent data suggest that artemisinin resistance has developed. [40][41][42][43] It would seem that enrolment parasitemia significantly influenced the parasite clearance times. Thus, high parasitemias were associated with a longer parasite clearance times.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Efficacies of Artemisinin-Based Combination Therapies in Nigerian Children with Uncomplicated Falciparum Malaria during Five Years of Adoption as First-Line Treatments

Gbotosho

Sowunmi²,

Happi³

et al. 2011

The American Society of Tropical Medicine and Hygiene

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Abstract. The therapeutic efficacies of 3-day regimens of artesunate-amodiaquine and artemether-lumefantrine during 5 years of adoption as first-line treatments were evaluated in 811 ≤ 12-year-old malarious children. Compared with artemether-lumefantrine, amodiaquine-artesunate significantly reduced the proportion of children with fever and parasitemia 1 day after treatment (day 1; P < 0.008 for both). The proportion of parasitemic children on day 2 and gametocytemia on presentation and carriage reduced significantly over the years ( P < 0.000001 and P < 0.03, respectively; test for trend). Overall efficacy was 96.5% (95% confidence interval [CI] = 94.5-98.6) and remained unchanged over the years ( P = 0.87; test for trend). Kinetics of parasitemias after treatments were estimated by a non-compartmental model. Declines of parasitemias were monoexponential, with a mean elimination half-life of 1.09 hours (95% CI = 1.0-1.16). Parasitemia half-lives and efficacy were similar for both regimens and in all ages. Artesunate-amodiaquine and artemether-lumefantrine remain efficacious treatments of uncomplicated falciparum malaria in Nigerian children 5 years after adoption.

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“…This achievement is owed to a rise in investments for vector control such as the use of Insecticide Treated Bed Nets (ITNs), and treatment including Intermittent Preventive Treatment during pregnancy (IPTp) and combined therapies, especially Artemisinin-Based Combined Therapies (ACTs) against uncomplicated malaria [6][7][8]. However, these successes are threatened by the emergence of parasite resistance against artemisinin [9][10][11]. Moreover, this resistance was firmly established in Cambodia, Thailand, Vietnam and Burma and its possible spread over the rest of South-east Asia has been documented [12,13].…”

Section: Introductionmentioning

confidence: 99%