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Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis

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 ORCID: https://orcid.org/0000-0003-3405-6638, 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, Elzaki, Salah-Eldin G, Eziefula, Alice C, Kariuki, Simon, Kwambai, Titus K, Maestre, Amanda E, Martensson, Andreas, Mosha, Dominic, Mwaiswelo, Richard O, Ngasala, Billy E, Okebe, Joseph, Roh, Michelle E, Sawa, Patrick, Tiono, Alfred B, Chen, Ingrid, Drakeley, Chris J and Bousema, Teun (2020) 'Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis'. Journal of Infectious Disease, Issue jiaa498. (In Press)

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Abstract

Background
Since the World Health Organization recommended single low-dose (0.25mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant P. falciparum, several single-site studies have been conducted to assess its efficacy.

Methods
An individual patient meta-analysis to assess the gametocytocidal and transmission-blocking efficacy of PQ used in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (i) gametocyte carriage in the first two weeks post-treatment; (ii) the probability of infecting at least one mosquito or of a mosquito becoming infected.

Results
In 2,574 participants from fourteen studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytaemia on day 0 (Odds Ratio (OR)=0.22; 95%CI 0.17-0.28 and OR=0.12; 95%CI 0.08–0.16, respectively). The rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (p=0.010 for day 7). Addition of 0.25mg/kg PQ was associated with near complete prevention of transmission to mosquitoes.

Conclusion
Primaquine’s transmission-blocking effects are achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP.

Item Type: Article
Subjects: QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 256 Antimalarials
QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 258 Primaquine. Quinacrine
QX Parasitology > Protozoa > QX 135 Plasmodia
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1093/infdis/jiaa498
Depositing User: Stacy Murtagh
Date Deposited: 12 Aug 2020 13:15
Last Modified: 29 Oct 2020 12:00
URI: https://archive.lstmed.ac.uk/id/eprint/15306

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