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The gametocytocidal efficacy of different single doses of primaquine with dihydroartemisinin-piperaquine in asymptomatic parasite carriers in the Gambia

Tijdschriftbijdrage - Tijdschriftartikel

Ondertitel:a randomized controlled trial
Background: Asymptomatic low-density gametocyte carriers represent the majority of malaria-infected individuals. However, the impact of recommended treatment with single low dose of primaquine and an artemisininbased combination therapy to reduce transmission in this group is unknown. Methods: This was a four-arm, open label, randomized controlled trial comparing the effect of dihydroartemisinin-piperaquine (DHAP) alone or combined with single dose of primaquine (PQ) at 0.20 mg/kg, 0.40 mg/kg, or 0.75 mg/kg on Plasmodium falciparum gametocytaemia, infectiousness to mosquitoes and hemoglobin change in asymptomatic, malaria-infected, glucose-6-phosphate dehydrogenase (G6PD) normal individuals. Randomization was done using a computer-generated sequence of uneven block sizes with codes concealed in sequentially numbered opaque envelopes. The primary endpoint was the prevalence of P. falciparum gametocytemia at day 7 of follow-up determined by quantitative nucleic acid sequence based assay and analysis was by intention to treat. The trial has been concluded (registration number: NCT01838902; https://clinicaltrials.gov/ct2/show/NCT01838902). Results: A total of 694 asymptomatic, malaria-infected individualswere enrolled. Gametocyte prevalence at day 7 was 37.0% (54/146; 95% CI 29.245.4), 19.0% (27/142; 95% CI 12.926.4), 17.2% (25/145; 95% CI 11.023.5) and 10.6% (15/141; 95% CI 6.116.9) in the DHAP alone, 0.20 mg/kg, 0.40 mg/kg, and 0.75 mg/kg PQ arms, respectively. The main adverse events reported include headache (130/471, 27.6%), cough (73/471, 15.5%), history of fever (61/471, 13.0%) and abdominal pain (57/471, 12.1%). There were five serious adverse events however, none was related to the interventions. Interpretation: A single course of PQ significantly reduces gametocyte carriage in malaria-infected asymptomatic, G6PD-normal individuals without increasing the risk of clinical anemia. The limited number of successful mosquito infections suggests that post-treatment transmission potential in this asymptomatic population is low.
Tijdschrift: EBioMedicine
ISSN: 2352-3964
Volume: 13
Pagina's: 348 - 355
Jaar van publicatie:2016