Parasite clearance rates in Upper Myanmar indicate a distinctive artemisinin resistance phenotype: a therapeutic efficacy study

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 pr...

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Published in:Malaria journal Vol. 15; no. 1; p. 185
Main Authors: Tun, Kyaw Myo, Jeeyapant, Atthanee, Imwong, Mallika, Thein, Min, Aung, Sai Soe Moe, Hlaing, Tin Maung, Yuentrakul, Prayoon, Promnarate, Cholrawee, Dhorda, Mehul, Woodrow, Charles J., Dondorp, Arjen M., Ashley, Elizabeth A., Smithuis, Frank M., White, Nicholas J., Day, Nicholas P. J.
Format: Journal Article
Language:English
Published: London BioMed Central 31.03.2016
BioMed Central Ltd
Springer Nature B.V
Subjects:
Administration, Oral
Adolescent
Adult
Aged
Analysis
Antimalarials - therapeutic use
Artemisinins - therapeutic use
Biomedical and Life Sciences
Biomedicine
Care and treatment
Child
Child, Preschool
Dosage and administration
Drug Resistance
Entomology
Female
Genotypes
Health aspects
Humans
Infant
Infectious Diseases
Malaria
Malaria, Falciparum - drug therapy
Malaria, Falciparum - parasitology
Male
Microbiology
Middle Aged
Mutation
Mutation, Missense
Myanmar
Parasitemia - drug therapy
Parasitemia - parasitology
Parasites
Parasitology
Plasmodium falciparum
Primaquine
Prospective Studies
Protozoan Proteins - genetics
Public Health
Quinolines - therapeutic use
Tropical Medicine
Vector-borne diseases
Young Adult
Myanmar
Cambodia
China
Artemisinin resistance
Myanmar
Parasite clearance half-life
Kelch 13 propeller
Plasmodium falciparum
ISSN:1475-2875, 1475-2875
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Summary: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 half-life 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.
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ISSN:1475-2875
1475-2875
DOI:10.1186/s12936-016-1240-7