Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium <i>falciparum</i> Gametocytes and Transmission: An Individual Patient Meta-Analysis
Kasia Stepniewska, Georgina Humphreys, Bronner P. Gonçalves, Elaine Craig, Roly Gosling, Philippe J. Guérin, Ric N. Price, Karen I. Barnes, Jaishree Raman, Menno R. Smit, Umberto D’Alessandro, William J. Stone, Anders Björkman, Aaron M. Samuels, Maria I Arroyo-Arroyo, Guido J. H. Bastiaens, Joelle Brown, Alassane Dicko, Badria El-Sayed, Salah-Eldin El-Zaki, Alice C Eziefula, Simon Kariuki, Titus K. Kwambai, Amanda Elena Maestre, Andreas Mårtensson, Dominic Mosha, Richard Mwaiswelo, Billy Ngasala, Joseph Okebe, Michelle E Roh, Patrick Sawa, Alfred B. Tiono, Ingrid Chen, Chris Drakeley, Teun Bousema
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.