Piperaquine Monotherapy of Drug-Susceptible Plasmodium falciparum Infection Results in Rapid Clearance of Parasitemia but Is Followed by the Appearance of …
CJ Pasay, R Rockett, S Sekuloski… - The Journal of …, 2016 - academic.oup.com
The Journal of infectious diseases, 2016•academic.oup.com
Background. Piperaquine, coformulated with dihydroartemisinin, is a component of a widely
used artemisinin combination therapy. There is a paucity of data on its antimalarial activity
as a single agent. Such data, if available, would inform selection of new coformulations.
Methods. We undertook a study in healthy subjects, using the induced blood stage malaria
(IBSM) model to test the antimalarial activity of single doses of piperaquine (960, 640, and
480 mg) in 3 cohorts. In a pilot study in the third cohort, gametocyte clearance following …
used artemisinin combination therapy. There is a paucity of data on its antimalarial activity
as a single agent. Such data, if available, would inform selection of new coformulations.
Methods. We undertook a study in healthy subjects, using the induced blood stage malaria
(IBSM) model to test the antimalarial activity of single doses of piperaquine (960, 640, and
480 mg) in 3 cohorts. In a pilot study in the third cohort, gametocyte clearance following …
Abstract
Background. Piperaquine, coformulated with dihydroartemisinin, is a component of a widely used artemisinin combination therapy. There is a paucity of data on its antimalarial activity as a single agent. Such data, if available, would inform selection of new coformulations.
Methods. We undertook a study in healthy subjects, using the induced blood stage malaria (IBSM) model to test the antimalarial activity of single doses of piperaquine (960, 640, and 480 mg) in 3 cohorts. In a pilot study in the third cohort, gametocyte clearance following administration of 15 mg, or 45 mg or no primaquine was investigated.
Results. Parasite clearance over the 48-hour period after piperaquine administration was more rapid in the 960 mg cohort, compared with the 640 mg cohort (parasite reduction ratio, 2951 [95% confidence interval {CI}, 1520–5728] vs 586 [95% CI, 351–978]; P < .001). All 24 subjects developed gametocytemia as determined by pfs25 transcripts. Clearance of pfs25 was significantly faster in those receiving primaquine than in those not receiving primaquine (P < .001).
Conclusions. Piperaquine possesses rapid parasite-clearing activity, but monotherapy is followed by the appearance of gametocytemia, which could facilitate the spread of malaria. This new information should be taken into account when developing future antimalarial coformulations.
Clinical Trials Registration ACTRN12613000565741.
Oxford University Press