Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis
Stepniewska K., Humphreys GS., Gonçalves BP., Craig E., Gosling R., Guerin PJ., Price RN., Barnes KI., Raman J., Smit MR., D’Alessandro U., Stone WJR., Bjorkman A., Samuels AM., Arroyo-Arroyo MI., Bastiaens GJH., Brown JM., Dicko A., El-Sayed BB., Elzaki S-EG., Eziefula AC., Kariuki S., Kwambai TK., Maestre AE., Martensson A., Mosha D., Mwaiswelo RO., Ngasala BE., Okebe J., Roh ME., Sawa P., Tiono AB., Chen I., Drakeley CJ., Bousema T.
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Since the World Health Organization recommended single low-dose (0.25 mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant Plasmodium falciparum, several single-site studies have been conducted to assess efficacy.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>An individual patient meta-analysis to assess gametocytocidal and transmission-blocking efficacy of PQ in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (1) gametocyte carriage in the first 2 weeks post treatment; and (2) the probability of infecting at least 1 mosquito or of a mosquito becoming infected.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>In 2574 participants from 14 studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytemia on day 0 (odds ratio [OR], 0.22; 95% confidence interval [CI], .17–.28 and OR, 0.12; 95% CI, .08–.16, respectively). Rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (P = .010 for day 7). Addition of 0.25 mg/kg PQ was associated with near complete prevention of transmission to mosquitoes.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Transmission blocking is achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP.</jats:p> </jats:sec>