Primaquine dose and the risk of haemolysis in patients with uncomplicated Plasmodium vivax malaria: a systematic review and individual patient data meta-analysis

Rajasekhar, Megha; Simpson, Julie A; Ley, Benedikt; Edler, Peta; Chu, Cindy S; Abreha, Tesfay; Awab, Ghulam R; Baird, J Kevin; Bancone, Germana; Barber, Bridget E; Grigg, Matthew J; Hwang, Jimee; Karunajeewa, Harin; Lacerda, Marcus V G; Ladeia-Andrade, Simone; Llanos-Cuentas, Alejandro; Pukrittayakamee, Sasithon; Rijal, Komal R; Saravu, Kavitha; Sutanto, Inge; Taylor, Walter R J; Thriemer, Kamala; Watson, James A; Guerin, Philippe J; White, Nicholas J; Price, Ric N; Commons, Robert J; Adhikari, Bipin; Alam, Mohammad Shafiul; Anstey, Nicholas M; Assefa, Ashenafi; Boyd, Sarah C; Chau, Nguyen Hoang; Day, Nicholas PJ; Degaga, Tamiru Shibiru; Dondorp, Arjen M; Ferreira, Marcelo Urbano; Ghimire, Prakash; Green, Justin A; Khan, Wasif Ali; Koh, Gavin CKW; Mekuria, Asrat Hailu; Naadim, Mohammad Nader; Nelwan, Erni J; Nosten, Francois; Pasaribu, Ayodhia Pitaloka; Price, David J; Stepniewska, Kasia; von Seidlein, Lorenz; William, Timothy; Woodrow, Charles J; Woyessa, Adugna

doi:10.1016/s1473-3099(23)00431-0

Cited by 15 publications

(9 citation statements)

References 40 publications

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“… 53 The haematological safety of different primaquine doses and their association with G6PD activity are presented in a separate systematic review and individual patient data meta-analysis. 54 …”

Section: Discussionmentioning

confidence: 99%

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Effect of primaquine dose on the risk of recurrence in patients with uncomplicated Plasmodium vivax: a systematic review and individual patient data meta-analysis

Commons,

Rajasekhar,

Edler

et al. 2024

The Lancet Infectious Diseases

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Section: Discussionmentioning

confidence: 99%

“…Doses of 0·5 mg/kg per day were tolerated similarly to 0·25 mg/kg per day, but the benefit of increasing the daily dose to 1 mg/kg needs to be weighed against increases in gastrointestinal symptoms and the potential for haemolysis. 54 …”

Section: Discussionmentioning

confidence: 99%

Effect of primaquine dose on the risk of recurrence in patients with uncomplicated Plasmodium vivax: a systematic review and individual patient data meta-analysis

Commons,

Rajasekhar,

Edler

et al. 2024

The Lancet Infectious Diseases

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“…Defining acceptable tolerability of non-life-threatening events such as gastro-intestinal disturbance is even more difficult. More recent data however further support the use of higher primaquine doses in settings where G6PD testing can be provided [ 14 , 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Optimizing test and treat options for vivax malaria: An options assessment toolkit (OAT) for Asia Pacific national malaria control programs

Acharya,

Shrestha,

Thang

et al. 2024

PLOS Glob Public Health

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Designing policy in public health is a complex process requiring decision making that incorporates available evidence and is suitable to a country’s epidemiological and health system context. The main objective of this study was to develop an options assessment toolkit (OAT) to provide a pragmatic and evidence-based approach to the development of policies for the radical cure (prevention of relapse) of vivax malaria for national malaria control programs in the Asia-Pacific region. The OAT was developed using participatory research methods and a Delphi process using a sequential multi-phase design, adapted with a pre-development phase, a development phase, and a final development phase. In the pre-development phase, a literature review was conducted to inform the toolkit development. Data collection in the development phase consisted of core research team discussions, multiple rounds of consultation with participants from National Malaria Control Programs (NMP) (online and in person), and two separate modified e-Delphi processes with experts. The final development phase was the piloting of the toolkit during the annual meeting of the Asia Pacific Malaria Elimination Network (APMEN) Vivax Working Group. We developed a tool kit containing the following elements: i) Baseline Assessment Tool (BAT) to assess the readiness of NMPs for new or improved coverage of radical cure, ii) eight scenarios representative of Asia Pacific region, iii) matching test and treat options based on available options for G6PD testing and radical cure for the given scenarios, iv) an approaches tool to allow NMPs to visualize considerations for policy change process and different implementation strategies/approaches for each test and treat option. The OAT can support vivax radical cure policy formulation among NMPs and stakeholders tailoring for their unique country context. Future studies are needed to assess the utility and practicality of using the OAT for specific country context.

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“…A pooled analysis including 3421 patients from 29 studies found that the nadir Hb was similar in patients with G6PD activity ≥30% treated with and without primaquine at a population level 48. A subsequent individual patient data meta-analysis of 5462 patients found a similar risk of haemolysis in patients with ≥30% G6PD activity who were treated with 0.25 mg/kg/day or 0.5 mg/kg/day primaquine compared with patients treated without primaquine 49…”

Section: Discussionmentioning

confidence: 99%

“…data meta-analysis of 5462 patients found a similar risk of haemolysis in patients with ≥30% G6PD activity who were treated with 0.25 mg/kg/day or 0.5 mg/kg/day primaquine compared with patients treated without primaquine. 49 The relapse behaviour of P. vivax varies between regions. P. vivax in South Asia has a biphasic phenotype where the duration between initial infection and subsequent relapse is generally either around 1-2 months or >6 months.…”

Section: Bmj Global Healthmentioning

confidence: 99%

Safety and efficacy of primaquine in patients withPlasmodium vivaxmalaria from South Asia: a systematic review and individual patient data meta-analysis

Verma,

Commons,

Gupta

et al. 2023

BMJ Glob Health

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BackgroundThe optimal dosing of primaquine to prevent relapsingPlasmodium vivaxmalaria in South Asia remains unclear. We investigated the efficacy and safety of different primaquine regimens to preventP. vivaxrelapse.MethodsA systematic review identifiedP. vivaxefficacy 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 ofP. vivaxrecurrence 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.ResultsIn 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 ofP. vivaxrecurrences 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.ConclusionsPrimaquine treatment led to a marked decrease inP. vivaxrecurrences following low (~3.5 mg/kg) and high (~7 mg/kg) total doses, with no reported severe haemolytic events.PROSPERO registration numberCRD42022313730.

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Primaquine dose and the risk of haemolysis in patients with uncomplicated Plasmodium vivax malaria: a systematic review and individual patient data meta-analysis

Cited by 15 publications

References 40 publications

Effect of primaquine dose on the risk of recurrence in patients with uncomplicated Plasmodium vivax: a systematic review and individual patient data meta-analysis

Effect of primaquine dose on the risk of recurrence in patients with uncomplicated Plasmodium vivax: a systematic review and individual patient data meta-analysis

Optimizing test and treat options for vivax malaria: An options assessment toolkit (OAT) for Asia Pacific national malaria control programs

Safety and efficacy of primaquine in patients withPlasmodium vivaxmalaria from South Asia: a systematic review and individual patient data meta-analysis

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