Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 214, Issue 1, Pages 105-113Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiw128
Keywords
P. falciparum; malaria; piperaquine clinical trial; gametocytemia
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Funding
- Medicines for Malaria Venture
- Government of Queensland
- National Health Medical and Research Council [1041802]
- Wellcome Trust [095909/Z/11/Z]
- Wellcome Trust [095909/Z/11/Z] Funding Source: Wellcome Trust
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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.
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