Single low dose primaquine to reduce gametocyte carriage and Plasmodium falciparum transmission after artemether-lumefantrine in children with asymptomatic infection: a randomised, double-blind, placebo-controlled trial

BMC Medicine

Research Article

Alphonse Ouédraogo¹  Wamdaogo M. Guelbéogo¹  Sodiomon B. Sirima¹  Edith C. Bougouma¹  Amidou Diarra¹  Débé Siaka¹  Issa Nebie¹  Alfred B. Tiono¹  Bronner P. Gonçalves²  Alice C. Eziefula²  Chris Drakeley²  Kjerstin Lanke³  Helmi Pett³  Teun Bousema³  John Bradley⁴ 

[1] Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso;Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK;Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands;MRC Tropical Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK;

关键词: Malaria;    Transmission;    Gametocytes;    Primaquine;    Artemisinin-based combination therapies;   

DOI  :  10.1186/s12916-016-0581-y

 received in 2015-11-25, accepted in 2016-02-12,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundA single low dose (0.25 mg/kg) of primaquine is recommended as a gametocytocide in combination with artemisinin-based combination therapies for Plasmodium falciparum but its effect on post-treatment gametocyte circulation and infectiousness to mosquitoes has not been quantified.MethodsIn this randomised, double-blind, placebo-controlled trial, 360 asymptomatic parasitaemic children aged 2-15 years were enrolled and assigned to receive: artemether-lumefantrine (AL) and a dose of placebo; AL and a 0.25 mg/kg primaquine dose; or AL and a 0.40 mg/kg primaquine dose. On days 0, 2, 3, 7, 10 and 14, gametocytes were detected and quantified by microscopy, Pfs25 mRNA quantitative nucleic acid sequence based amplification (QT-NASBA), and quantitative reverse-transcriptase PCR (qRT-PCR). For a subset of participants, pre- and post-treatment infectiousness was assessed by mosquito feeding assays on days -1, 3, 7, 10 and 14.ResultsBoth primaquine arms had lower gametocyte prevalences after day 3 compared to the placebo arm, regardless of gametocyte detection method. The mean (95 % confidence interval) number of days to gametocyte clearance in children with patent gametocytes on day 0 (N = 150) was 19.7 (14.6 – 24.8), 7.7 (6.3 – 9.1) and 8.2 (6.7 – 9.6) for the AL-placebo, the 0.25 mg/kg primaquine dose and the 0.40 mg/kg primaquine dose arms, respectively. While 38.0 % (30/79) of selected gametocytaemic individuals were infectious before treatment, only 1/251 participant, from the AL-placebo group, infected mosquitoes after treatment.ConclusionsWe observed similar gametocyte clearance rates after 0.25 and 0.40 mg/kg primaquine doses. Infectivity to mosquitoes after AL was very low and absent in primaquine arms.ClinicalTrials.gov RegistrationNCT01935882

【 授权许可】

CC BY   
© Gonçalves et al. 2016