Primaquine (PQ) is currently the only available drug that can clear mature transmission
stages of P. falciparum parasites. PQ was previously shown to clear gametocytes that persist
after artemisinin-combination therapy. However, there are safety concerns about the use of PQ
at the currently recommended dose of 0.75mg/kg in individuals who are glucose-6-phosphate
dehydrogenase (G6PD) deficient. PQ causes transient but significant haemolysis in G6PD
deficient individuals; this side-effect is dose dependent. There are indications that a lower
dosing of PQ may effectively reduce gametocyte carriage but the lowest efficacious dose for
gametocyte clearance is currently unknown. Recently, the World Health Organization changed
their recommendation to a low dose of primaquine, 0.25mg/kg. However, there is no direct
evidence on the extent to which (low dose) PQ prevents malaria transmission to mosquitoes and
what the lowest efficacious dose is.
In the current study we aim to identify the lowest efficacious dose of PQ in individuals with
normal G6PD function. Children with asymptomatic malaria and normal G6PD enzyme function will
be randomized to treatment with artemether-lumefantrine alone or in combination with low
doses of PQ. All enrolled individuals will receive a full three-day course of AL, and will be
randomized to receive a dose of primaquine or placebo with their fifth dose of AL. Efficacy
will be determined based on gametocyte carriage during follow-up, measured by molecular
methods. For a subset of participants with patent gametocytes, primaquine effect on
infectivity to mosquitoes will be assessed by membrane feeding assays
Phase:
Phase 2/Phase 3
Details
Lead Sponsor:
London School of Hygiene and Tropical Medicine
Collaborators:
Centre national de recherche et de formation sur le paludisme Radboud University
Treatments:
Artemether Artemether-lumefantrine combination Artemether, Lumefantrine Drug Combination Artemisinins Lumefantrine Primaquine