Piperaquine monotherapy of drug sensitive P. falciparum infection results in rapid clearance of parasitaemia but is followed by the appearance of gametocytemia

Pasay, Cielo J., Rockett, Rebecca, Sekuloski, Silvana, Griffin, Paul, Marquart, Louise, Peatey, Christopher, Wang, Claire Y. T., O'Rourke, Peter, Elliott, Suzanne, Baker, Mark, Mohrle, Jorg J. and McCarthy, James S. (2016) Piperaquine monotherapy of drug sensitive P. falciparum infection results in rapid clearance of parasitaemia but is followed by the appearance of gametocytemia. The Journal of Infectious Diseases, 214 1: 105-113. doi:10.1093/infdis/jiw128


Author Pasay, Cielo J.
Rockett, Rebecca
Sekuloski, Silvana
Griffin, Paul
Marquart, Louise
Peatey, Christopher
Wang, Claire Y. T.
O'Rourke, Peter
Elliott, Suzanne
Baker, Mark
Mohrle, Jorg J.
McCarthy, James S.
Title Piperaquine monotherapy of drug sensitive P. falciparum infection results in rapid clearance of parasitaemia but is followed by the appearance of gametocytemia
Formatted title
Piperaquine monotherapy of drug sensitive Plasmodium falciparum infection results in rapid clearance of parasitaemia but is followed by the appearance of gametocytemia
Journal name The Journal of Infectious Diseases   Check publisher's open access policy
ISSN 1537-6613
0022-1899
Publication date 2016-07-01
Year available 2016
Sub-type Article (original research)
DOI 10.1093/infdis/jiw128
Open Access Status DOI
Volume 214
Issue 1
Start page 105
End page 113
Total pages 9
Place of publication Cary, NC United States
Publisher Oxford University Press
Collection year 2017
Language eng
Formatted 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.
Keyword P. falciparum
Malaria
Piperaquine clinical trial
Gametocytemia
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
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Created: Mon, 25 Apr 2016, 11:30:24 EST by Paul Griffin on behalf of Medicine - Mater Hospital