Stepniewska, Kasia, Humphreys, Georgina S, Gonçalves, Bronner P, Craig, Elaine, Gosling, Roly, Guerin, Philippe J, Price, Ric N, Barnes, Karen I, Raman, Jaishree, Smit, Menno R, D'Alessandro, Umberto, Stone, Will J R, Bjorkman, Anders, Samuels, Aaron M, Arroyo-Arroyo, Maria I, Bastiaens, Guido J H, Brown, Joelle M, Dicko, Alassane, El-Sayed, Badria B, and Elzaki, Salah-Eldin G
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. [ABSTRACT FROM AUTHOR]