Cochrane: 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 searched the literature up to 05 January 2015 and included
17 randomized controlled trials (RCTs) and one quasi-RCT.
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 glucose-6-phosphate dehydrogenase (G6PD) deficiency, an enzyme deficiency common in many malaria endemic settings. In these people, high doses of primaquine given over several days damages red blood cells and causes anaemia, and sometimes these events may be life-threatening.
The World Health Organization (WHO) recommends adding a single dose of primaquine to falciparum malaria treatment with the intention of reducing malaria transmission and to contribute to malaria elimination. In 2013, the WHO amended their guideline, reducing the PQ dose from 0.75 mg/kg to 0.25 mg/kg to reduce the risk of haemolysis, combined with indirect evidence suggesting this was as effective as the higher dose.
What the research says
We found no eligible studies that tested whether primaquine added to malaria treatment reduces community transmission of malaria.
When added to currently recommended 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 of the human host to mosquitoes (defined as the period that gametocytes are detected circulating in the blood) when given at doses greater than 0.6 mg/kg (high quality evidence) and at doses between 0.4 and 0.6 mg/kg (moderate quality evidence). We only found one study using 0.1 mg/kg with an estimate consistent with a smaller reduction in gametocytes, but the analysis was underpowered and did not reach statistical significance (low quality evidence).
In older studies when used with treatments not currently recommended, 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). No studies examined primaquine using the low dose currently recommended.
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 dosing levels currently recommended.
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 glucose-6-phosphate dehydrogenase (G6PD) deficiency, an enzyme deficiency common in many malaria endemic settings. In these people, high doses of primaquine given over several days damages red blood cells and causes anaemia, and sometimes these events may be life-threatening.
The World Health Organization (WHO) recommends adding a single dose of primaquine to falciparum malaria treatment with the intention of reducing malaria transmission and to contribute to malaria elimination. In 2013, the WHO amended their guideline, reducing the PQ dose from 0.75 mg/kg to 0.25 mg/kg to reduce the risk of haemolysis, combined with indirect evidence suggesting this was as effective as the higher dose.
What the research says
We found no eligible studies that tested whether primaquine added to malaria treatment reduces community transmission of malaria.
When added to currently recommended 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 of the human host to mosquitoes (defined as the period that gametocytes are detected circulating in the blood) when given at doses greater than 0.6 mg/kg (high quality evidence) and at doses between 0.4 and 0.6 mg/kg (moderate quality evidence). We only found one study using 0.1 mg/kg with an estimate consistent with a smaller reduction in gametocytes, but the analysis was underpowered and did not reach statistical significance (low quality evidence).
In older studies when used with treatments not currently recommended, 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). No studies examined primaquine using the low dose currently recommended.
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 dosing levels currently recommended.
Authors' conclusions:
In individual patients, PQ added to malaria treatments reduces gametocyte prevalence, but this is based on trials using doses of
more than 0.4 mg/kg. Whether this translates into preventing people
transmitting malaria to mosquitoes has rarely been tested in controlled
trials, but there appeared to be a strong reduction in infectiousness in
the two small studies that evaluated this. No included trials evaluated
whether this policy has an impact on community malaria transmission.
For the currently recommended low dose regimen, there is currently little direct evidence to be confident that the effect of reduction in gametocyte prevalence is preserved, or that it is safe in people with G6PD deficiency.
For the currently recommended low dose regimen, there is currently little direct evidence to be confident that the effect of reduction in gametocyte prevalence is preserved, or that it is safe in people with G6PD deficiency.