Abstract
BackgroundSince 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.MethodsAn 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.ResultsIn 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.ConclusionsTransmission blocking is achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP.
Highlights
Background Since the World HealthOrganization 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 t efficacy. ip Methods cr An individual patient meta-analysis to assess the gametocytocidal and transmission-blocking efficacy s of PQ used in combination with different ACTs was conducted
To mitigate concerns related to haemolysis in individuals Ac with glucose-6-phosphate dehydrogenase deficiency (G6PDd) and based on efficacy shown at low doses, a single low-dose of 0.25mg/kg of PQ was recommended for the gametocytocidal indication [10]
Studies were eligible for the inclusion in this analysis if (i) individual patient data (IPD) came from a clinical efficacy trial of s patients with uncomplicated P. falciparum infection or asymptomatic parasite carriers containing at u least one study arm with a combination of a blood schizonticide and a single dose of PQ; (ii) patient n demographics and information on dosing of the blood schizonticide and PQ were available; a (iii) transmission potential was assessed by weekly gametocyte carriage using M molecular methods and/or by membrane feeding assay conducted on day 0 and any day postd treatment; (iv) patients were followed up at least until day 14
Summary
Background Since the World HealthOrganization 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 t efficacy. ip Methods cr An individual patient meta-analysis to assess the gametocytocidal and transmission-blocking efficacy s of PQ used in combination with different ACTs was conducted. 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 t efficacy. Ip Methods cr An individual patient meta-analysis to assess the gametocytocidal and transmission-blocking efficacy s of PQ used in combination with different ACTs was conducted. Gametocyte carriage can persist for several cr days and even weeks after ACT administration [3, 6] and treated individuals can continue to be a s source of mosquito infections [3, 7, 8].
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