We conducted a review of the effects of adding a single dose (or short
course) of primaquine to malaria treatment with the aim of reducing the
transmission of malaria. We included 17 randomized controlled trials and
one quasi-randomized controlled trial.
What is primaquine and how might it reduce transmission
Primaquine is an antimalarial drug which does not cure malaria illness,
but is known to kill the gametocyte stage of the malaria parasite which
infects mosquitoes when they bite humans. Primaquine is also known to
have potentially serious side effects in people with an enzyme
deficiency common in many malaria endemic settings (glucose-6-phosphate
dehydrogenase (G6PD) deficiency). In these people, high doses of
primaquine given over several days sometimes destroys red blood cells,
causing anaemia and, in some cases, possibly life-threatening effects.
The World Health Organization (WHO) recommends adding a single dose of
primaquine to malaria treatment with the intention of reducing malaria
transmission and to contribute to malaria elimination. This
recommendation was made in 2010, but in 2013 the WHO amended its
recommendation from a dose of 0.75 mg/kg to 0.25 mg/kg due to concerns
about safety, and indirect evidence suggesting this was as effective as
the higher dose.This review examines the evidence of benefits and harms
of using primaquine in this way, and looks for evidence that primaquine
will reduce malaria transmission in communities.
What the research says
We did not find any studies that tested whether primaquine added to
malaria treatment reduces the community transmission of malaria.
When added to current treatments for malaria (artemisinin-based
combination therapy), we found no studies evaluating the effects of
primaquine on the number of mosquitoes infected. However, primaquine
does reduce the duration of infectiousness (the period that gametocytes
are detected circulating in the blood) when given at doses of 0.4 mg/kg
or above (high quality evidence). We only found one study using 0.1
mg/kg but this study did not conclusively show that primaquine was still
effective at this dose (low quality evidence).
When added to older treatments for malaria, two studies showed that
primaquine at doses of 0.75 mg/kg reduced the number of mosquitoes
infected after biting humans (low quality evidence). Doses above 0.4
mg/kg reduced the duration of detectable gametocytes (high quality
evidence), but in a single study of the currently recommended 0.25 mg/kg
no effect was demonstrated (very low quality evidence).
Some studies excluded patients with G6PD deficiency, some included them,
and some did not comment. Overall the safety of PQ given as a single
dose was poorly evaluated across all studies, so these data do not
demonstrate whether the drug is safe or potentially harmful at this
Graves, P.M.; Gelband, H.; Garner, P. Primaquine or other 8-aminoquinoline for reducing P. falciparum transmission. Cochrane Database of Systematic Reviews (2014) Issue 6, Art. No.: CD008152. [DOI: 10.1002/14651858.CD008152.pub3]
Primaquine or other 8-aminoquinoline for reducing P. falciparum transmission