• Article

A non-randomized controlled trial of artesunate plus sulfadoxine-pyrimethamine with or without primaquine for preventing the post-treatment circulation of Plasmodium falciparum gametocytes

Artemisinin combination therapies eliminate immature Plasmodium falciparum gametocytes but not mature gametocytes,
which may persist for up to 1 month posttreatment. A single dose of primaquine, which is inexpensive and effective against mature
gametocytes, could be added to further reduce the potential for posttreatment parasite transmission. Currently, we have few
data regarding the effectiveness or safety of doing so. We collected data from 21 therapeutic efficacy trials of the National Antimalarial
Drug Resistance Monitoring System of India conducted during 2009 to 2010, wherein 9 sites used single-dose primaquine
(0.75 mg/kg of body weight) administered on day 2 along with artesunate plus sulfadoxine-pyrimethamine (ASSP) while
12 did not. We estimated the effect of primaquine on posttreatment gametocyte clearance and the total number of gametocyteweeks
as determined by microscopy. We compared the median area under the curve for gametocyte density and reported adverse
events. One thousand three hundred thirty-five patients completed the antimalarial drug treatment. Adjusting for region, primaquine
increased the rate of gametocyte clearance (hazard ratio, 1.9; 95% confidence interval [CI], 1.1 to 3.3), prevented 45%
(95% CI, 19 to 62) of posttreatment gametocyte-weeks, and decreased the area under the gametocyte density curve over the 28-
day follow-up compared to ASSP alone (P value0.01). The results were robust to other adjustment sets, and the estimated
effect of primaquine increased during sensitivity analysis on the measurement of exposure time. No serious adverse events were
detected. In conclusion, the addition of primaquine to ASSP was effective in reducing the posttreatment presence of P. falciparum
gametocytes. Primaquine was well tolerated and could be administered along with an artemisinin combination therapy as
the first-line therapy.

Citation

Shah, N. K., Schapira, A., Juliano, J. J., Srivastava, B., Macdonald, P., Poole, C., ... Mishra, N. (2013). A non-randomized controlled trial of artesunate plus sulfadoxine-pyrimethamine with or without primaquine for preventing the post-treatment circulation of Plasmodium falciparum gametocytes. Antimicrobial Agents and Chemotherapy, 57(7), 2948 - 54. DOI: 10.1128/AAC.00139-13

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