Primaquine or other 8-aminoquinoline for reducing Plasmodium falciparum transmission

A single dose of primaquine added to malaria treatment to prevent malaria transmission

Patricia M Graves1,2, Hellen Gelband3, Paul Garner4

EpiVec Consulting, Atlanta, USA 
James Cook University, School of Public Health, Tropical Medicine and Rehabilitation Sciences, Cairns, Queensland, Australia
Center for Disease Dynamics, Economics & Policy, Washington, DC, USA
4 Liverpool School of Tropical Medicine, International Health Group, Liverpool, Merseyside, UK

Primaquine or other 8-aminoquinoline for reducing Plasmodium falciparum transmission. Cochrane Database of Systematic Reviews 2015, Issue 2. Art. No.: CD008152.

To read the full review please follow this link: DOI: 10.1002/14651858.CD008152.pub4.

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.

Previous versions

Version 3
Primaquine or other 8-aminoquinoline for reducing P. falciparum transmission
Patricia M Graves, Hellen Gelband and Paul Garner
Article first published online: 30 JUN 2014 | DOI: 10.1002/14651858.CD008152.pub3

Version 2
Primaquine for reducing Plasmodium falciparum transmission
Patricia M Graves, Hellen Gelband and Paul Garner
Article first published online: 12 SEP 2012 | DOI: 10.1002/14651858.CD008152.pub2

Version 1
Primaquine for reducing transmission of Plasmodium falciparum malaria
Patricia M Graves, Hellen Gelband and Isabela Ribeiro
Article first published online: 7 OCT 2009 | DOI: 10.1002/14651858.CD008152