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Safety and efficacy of primaquine in patients with Plasmodium vivax malaria from South Asia: a systematic review and individual patient data meta-analysis

Abstract:

Background The optimal dosing of primaquine to prevent relapsing Plasmodium vivax malaria in South Asia remains unclear. We investigated the efficacy and safety of different primaquine regimens to prevent P. vivax relapse.

Methods A systematic review identified P. vivax efficacy studies from South Asia published between 1 January 2000 and 23 August 2021. In a one-stage meta-analysis of available individual patient data, the cumulative risks of P. vivax recurrence at day 42 and 180 were assessed by primaquine total mg/kg dose and duration. The risk of recurrence by day 180 was also determined in a two-stage meta-analysis. Patients with a >25% drop in haemoglobin to <70 g/L, or an absolute drop of >50 g/L between days 1 and 14 were categorised by daily mg/kg primaquine dose.

Results In 791 patients from 7 studies in the one-stage meta-analysis, the day 180 cumulative risk of recurrence was 61.1% (95% CI 42.2% to 80.4%; 201 patients; 25 recurrences) after treatment without primaquine, 28.8% (95% CI 8.2% to 74.1%; 398 patients; 4 recurrences) following low total (2 to <5 mg/kg) and 0% (96 patients; 0 recurrences) following high total dose primaquine (≥5 mg/kg). In the subsequent two-stage meta-analysis of nine studies (3529 patients), the pooled proportions of P. vivax recurrences by day 180 were 12.1% (95% CI 7.7% to 17.2%), 2.3% (95% CI 0.3% to 5.4%) and 0.7% (95% CI 0% to 6.1%), respectively. No patients had a >25% drop in haemoglobin to <70 g/L.

Conclusions Primaquine treatment led to a marked decrease in P. vivax recurrences following low (~3.5 mg/kg) and high (~7 mg/kg) total doses, with no reported severe haemolytic events.

PROSPERO registration number CRD42022313730.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1136/bmjgh-2023-012675

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Role:
Author
ORCID:
0000-0001-9870-6017
More by this author
Role:
Author
ORCID:
0000-0003-0932-0935


Publisher:
BMJ Publishing Group
Journal:
BMJ Global Health More from this journal
Volume:
8
Issue:
12
Article number:
e012675
Place of publication:
England
Publication date:
2023-12-20
Acceptance date:
2023-11-25
DOI:
EISSN:
2059-7908
Pmid:
38123228


Language:
English
Keywords:
Pubs id:
1586087
Local pid:
pubs:1586087
Deposit date:
2023-12-29

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