TY - JOUR
T1 - Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission
T2 - An Individual Patient Meta-Analysis
AU - Stepniewska, Kasia
AU - Humphreys, Georgina S.
AU - Gonçalves, Bronner P.
AU - Craig, Elaine
AU - Gosling, Roly
AU - Guerin, Philippe J.
AU - Price, Ric N.
AU - Barnes, Karen I.
AU - Raman, Jaishree
AU - Smit, Menno R.
AU - D'Alessandro, Umberto
AU - Stone, Will J.R.
AU - Bjorkman, Anders
AU - Samuels, Aaron M.
AU - Arroyo-Arroyo, Maria I.
AU - Bastiaens, Guido J.H.
AU - Brown, Joelle M.
AU - Dicko, Alassane
AU - El-Sayed, Badria B.
AU - Elzaki, Salah Eldin G.
AU - Eziefula, Alice C.
AU - Kariuki, Simon
AU - Kwambai, Titus K.
AU - Maestre, Amanda E.
AU - Martensson, Andreas
AU - Mosha, Dominic
AU - Mwaiswelo, Richard O.
AU - Ngasala, Billy E.
AU - Okebe, Joseph
AU - Roh, Michelle E.
AU - Sawa, Patrick
AU - Tiono, Alfred B.
AU - Chen, Ingrid
AU - Drakeley, Chris J.
AU - Bousema, Teun
N1 - Funding Information: This work was supported by the Bill and Melinda Gates Foundation (grant number OPP1089413) Publisher Copyright: © 2020 The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - 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.
AB - 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.
KW - Plasmodium falciparum
KW - gametocytemia
KW - single low-dose primaquine
UR - http://www.scopus.com/inward/record.url?scp=85128161481&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/infdis/jiaa498
DO - https://doi.org/10.1093/infdis/jiaa498
M3 - Article
C2 - 32778875
SN - 0022-1899
VL - 225
SP - 1215
EP - 1226
JO - Journal of infectious diseases
JF - Journal of infectious diseases
IS - 7
ER -