Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment

Verena Ilona Carrara, Julien Zwang, Elizabeth A. Ashley, Ric N. Price, Kasia Stepniewska, Marion Barends, Alan Brockman, Tim Anderson, Rose McGready, Lucy Phaiphun, Stephane Proux, Michele van Vugt, Robert Hutagalung, Khin Maung Lwin, Aung Pyae Phyo, Piyanuch Preechapornkul, Mallika Imwong, Sasithon Pukrittayakamee, Pratap Singhasivanon, Nicholas J. WhiteFrançois Nosten

    Research output: Contribution to journalReview articlepeer-review

    191 Scopus citations

    Abstract

    Background: Artemisinin combination treatments (ACT) are recommended as first line treatment for falciparum malaria throughout the malaria affected world. We reviewed the efficacy of a 3-day regimen of mefloquine and artesunate regimen (MAS3 ), over a 13 year period of continuous deployment as first-line treatment in camps for displaced persons and in clinics for migrant population along the Thai-Myanmar border. Methods and Findings: 3,264 patients were enrolled in prospective treatment trials between 1995 and 2007 and treated with MAS3. The proportion of patients with parasitaemia persisting on day-2 increased significantly from 4.5% before 2001 to 21.9% since 2002 (p<0.001). Delayed parasite clearance was associated with increased risk of developing gametocytaemia (AOR = 2.29; 95% CI, 2.00-2.69, p = 0.002). Gametocytaemia on admission and carriage also increased over the years (p = 0.001, test for trend, for both). MAS3 efficacy has declined slightly but significantly (Hazards ratio 1.13; 95% CI, 1.07-1.19, p<0.001), although efficacy in 2007 remained well within acceptable limits: 96.5% (95% CI, 91.0-98.7). The in vitro susceptibility of P. falciparum to artesunate increased significantly until 2002, but thereafter declined to levels close to those of 13 years ago (geometric mean in 2007: 4.2 nM/l; 95% CI, 3.2-5.5). The proportion of infections caused by parasites with increased pfmdr1 copy number rose from 30% (12/ 40) in 1996 to 53% (24/45) in 2006 (p = 0.012, test for trend). Conclusion: Artesunate-mefloquine remains a highly efficacious antimalarial treatment in this area despite 13 years of widespread intense deployment, but there is evidence of a modest increase in resistance. Of particular concern is the slowing of parasitological response to artesunate and the associated increase in gametocyte carriage.

    Original languageEnglish (US)
    Article numbere4551
    JournalPloS one
    Volume4
    Issue number2
    DOIs
    StatePublished - Feb 23 2009

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)
    • General

    Fingerprint Dive into the research topics of 'Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment'. Together they form a unique fingerprint.

    Cite this