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, BPORCID logo; Craig, E; Gosling, RORCID logo; Guerin, PJ; Price, RN; Barnes, KI; Raman, J; Smit, MR; +25 more...D'Alessandro, UORCID logo; Stone, WJORCID logo; Bjorkman, A; Samuels, AM; Arroyo-Arroyo, MI; Bastiaens, GJ; Brown, JM; Dicko, A; El-Sayed, BB; Elzaki, SG; 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, CJORCID logo; Bousema, TORCID logo and (2020) Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis. The Journal of infectious diseases, 225 (7). pp. 1215-1226. ISSN 0022-1899 DOI: 10.1093/infdis/jiaa498
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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.


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