Publication: Parasite clearance rates in Upper Myanmar indicate a distinctive artemisinin resistance phenotype: a therapeutic efficacy study
Issued Date
2016
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Language
eng
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Mahidol University
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BioMed Central
Bibliographic Citation
Malaria Journal. Vol.15, (2016), 185
Suggested Citation
Tun, Kyaw Myo, Atthanee Jeeyapant, Mallika Imwong, Min Thein, Sai Soe Moe Aung, Hlaing, Tin Maung, Prayoon Yuentrakul, Cholrawee Promnarate, Mehul Dhorda, Woodrow, Charles J., Dondorp, Arjen M., Ashley, Elizabeth A., Smithuis, Frank M., White, Nicholas J., Day, Nicholas P. J. Parasite clearance rates in Upper Myanmar indicate a distinctive artemisinin resistance phenotype: a therapeutic efficacy study. Malaria Journal. Vol.15, (2016), 185. doi:10.1186/s12936-016-1240-7 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/3150
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Title
Parasite clearance rates in Upper Myanmar indicate a distinctive artemisinin resistance phenotype: a therapeutic efficacy study
Abstract
Background: Artemisinin resistance in Plasmodium falciparum extends across Southeast Asia where it is associated
with worsening partner drug resistance and a decline in the efficacy of frontline artemisinin-based combination
therapy. Dihydroartemisinin-piperaquine (DP) is an essential component of preventive and curative treatment in the
region, but its therapeutic efficacy has fallen in Cambodia.
Methods: A prospective clinical and parasitological evaluation of DP was conducted at two sites in Upper Myanmar
between August 2013 and December 2014, enrolling 116 patients with acute uncomplicated falciparum malaria.
Patients received DP orally for 3 days together with primaquine 0.25 mg/kg on admission. Parasite clearance half-lives
based on 6 hourly blood smears, and day 42 therapeutic responses were assessed as well as parasite K13 genotypes.
Results: Median parasite clearance half-life was prolonged, and clearance half-life was greater than 5 h in 21 % of
patients. Delayed parasite clearance was significantly associated with mutations in the propeller region of the parasite
k13 gene. The k13 F446I mutation was found in 25.4 % of infections and was associated with a median clearance halflife
of 4.7 h compared with 2.7 h for infections without k13 mutations (p < 0.001). There were no failures after 42 days
of follow-up, although 18 % of patients had persistent parasitaemia on day 3.
Conclusion: The dominant k13 mutation observed in Upper Myanmar, F446I, appears to be associated with an
intermediate rate of parasite clearance compared to other common mutations described elsewhere in the Greater
Mekong Subregion. Discerning this phenotype requires relatively detailed clearance measurements, highlighting the
importance of methodology in assessing artemisinin resistance.