Primaquine at alternative dosing schedules for preventing relapse in people with Plasmodium vivax malaria

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Rachel Milligan1, André Daher,2 Patricia M Graves3

1. Cochrane Infectious Diseases Group, Liverpool School of Tropical Medicine, Liverpool, UK
2. Vice‐Presidency of Research and Biological Collections, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil, 
3. College of Public Health, Medical and Veterinary Sciences, James Cook University, Cairns, Australia

Milligan  R, Daher  A, Graves  PM. Primaquine at alternative dosing schedules for preventing relapse in people with   Plasmodium vivax malaria. Cochrane Database of Systematic Reviews 2019, Issue 7. Art. No.: CD012656. DOI: 10.1002/14651858.CD012656.pub2

Access the full text article here: DOI: 10.1002/14651858.CD012656.pub2.

Primaquine to cure people with Plasmodium vivax malaria: comparing dosing schedules

Plasmodium vivax malaria can sometimes cause potentially life‐threatening illness, and the infection continues to make many people unwell. The infection includes a liver stage, and this requires primaquine to eradicate it and prevent the infection recrudescing. However, the current dosing schedule requires 14 days of daily treatment.

What are the concerns about primaquine?

Primaquine is the only drug currently recommended to treat the liver parasites in P vivax malaria. It can cause anaemia in people with glucose‐6‐phosphate dehydrogenase (G6PD) deficiency, which is a relatively common genetic blood disorder. Shorter regimens would help reduce the risk of default with the current two‐week regimen.

What does the research say?

We summarized trials that compared the World Health Organization (WHO)‐recommended primaquine regimen of 15 to 30 mg per day for 14 days with the same or higher doses of primaquine given over different lengths of time to determine whether alternative regimens were as successful as the recommended courses at preventing future episodes of P vivax malaria. We searched for trials up to 17 December 2018, and included nine randomized controlled trials (studies in which participants are assigned to one of two or more treatment groups in a random manner) in our analysis.

When using 30 mg per day compared to 15 mg per day primaquine therapy for 14 days, we do not know if there is any difference in P vivax recurrences at 6 months (very low‐certainty evidence). No serious side effects were reported, but it is unclear whether or not there is a difference in other side effects between doses (very low‐certainty evidence).

When using 30 mg primaquine per day for 7 days compared to 15 mg per day for 14 days, there may be no difference in P vivaxrecurrences at 6 to 7 months (low‐certainty evidence). No serious adverse events were reported. There may be no difference in the number of side effects known to occur with primaquine between the two treatment regimens (low‐certainty evidence).

We do not know whether weekly primaquine increases or decreases recurrences of P vivax compared to the 14‐day regimen at 11 months' follow‐up (very low‐certainty evidence).

Further large high‐quality RCTs are needed, such as the IMPROV trial, to help improve the certainty of the evidence around alternative regimens.

How up‐to‐date is this review?

The review authors searched for studies up to 17 December 2018.