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Evidence supports WHO recommendation for PQ combined with ACTs to block Plasmodium falciparum transmission

12 February 2021

Evidence from a new study, initiated by the Primaquine Roll Out Group and conducted at WWARN, supports the World Health Organization (WHO) recommendation for use of 0.25mg/kg dose of primaquine (PQ) combined with artemisinin-based combination therapies (ACT) to block Plasmodium falciparum transmission.

The article, Efficacy of Single-Dose Primaquine with Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis, has been published in the Journal of Infectious Diseases.

This study was the first multi-site analysis to be undertaken since 2012 when the WHO recommended the administration of a single low-dose PQ in combination with ACTs in areas of low transmission or artemisinin-resistant Plasmodium falciparum. The recommendation was based on a number of single-site studies assessing efficacy.

This individual patient data (IPD) meta analysis, involving 2,574 participants across 14 studies and 9 countries, assessed gametocytocidal and transmission-blocking efficacy of PQ in combination with different ACTs. PQ doses between 0.0625 -0.75mg/kg were studied. Mixed effects logistic regression was used to quantify PQ effect on gametocyte carriage in the first 2 weeks post treatment; and on the probability of infecting at least one mosquito or of a mosquito becoming infected.

The findings confirmed the gametocyte clearing and sterilising effects of single dose PQ and provided evidence that the schizonticidal partner drug is a relevant consideration for optimal PQ dosing.  Specifically, the results showed the reduction in PCR-determined gametocyte carriage on days 7 and 14 was associated with PQ dose in nonlinear fashion and most apparent in patients presenting with gametocytemia on day 0. The rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine. In three studies with data from membrane feeding experiments, a dosage of 0.25 mg/kg PQ was associated with near complete prevention of transmission to mosquitoes.

In conclusion, the findings support the use of PQ as a potent gametocytocide and transmission-blocking tool for P. falciparum malaria.

 

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