Vivax malaria is associated with recurrent parasitaemia and anaemia with substantial attributable morbidity and mortality. Radical cure with an 8-aminoquinoline remains the only effective way to prevent relapsing vivax malaria. However, integration of 8-aminoquinolines into national malaria policy and widespread clinical use is hampered by differing efficacy and differing adverse event profiles of 8-aminoquinolines between regions; including differences in haemolysis related to varied proportions and phenotypes of G6PD deficiency within a population. Primaquine remains the main 8-aminoquinoline in widespread use and the only 8-aminoquinoline available for use with artemisinin-based combination therapies. 

The most efficacious and safe regimen of primaquine in Latin America remains unclear, with studies from different locations reporting varied efficacy. An in-depth review of available individual patient data will enable an improved understanding of the safety, tolerability and efficacy of differing primaquine radical cure regimens for the Latin American context; directly informing national malaria control policies.

1. To investigate the effect of daily primaquine mg/kg dose on drug tolerability in Latin America
2. To investigate haemolytic safety associated with primaquine use and dose in Latin America
3. To investigate the effect of total primaquine mg/kg dose and regimen duration on the risk of P. vivax recurrence in Latin America

Essential data/criteria

• Prospective clinical efficacy studies of uncomplicated vivax malaria with a minimum follow up of 28 days including at least one treatment arm with a daily primaquine regimen commenced within 28 days of schizontocidal treatment
• Treatment with chloroquine, one of five common artemisinin-based combination therapies (artemether-lumefantrine, artesunate-mefloquine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, artesunate-sulfadoxine-pyrimethamine) with or without primaquine administration
• Information on dose of schizontocidal treatment and use, timing, dose and duration of primaquine treatment
• Baseline data on patient age and sex
• Asexual parasite density at day 0 and reporting of parasite presence or absence during follow up

Desirable data/criteria

• Baseline weight
• Individual tablet or mg dosing
• Documentation on the supervision of drug administration
• Haemoglobin (hb) or haematocrit (hct) measured on day 0 and during follow-up
• Malnutrition as gauged by weight and age +/- height or middle upper arm circumference
• Qualitative or quantitative assessment of G6PD status
• History of malaria within the past 28 days
• History of fever within the last 24 hours at baseline and during follow up

Data on vomiting post administration

After upload to the WWARN Data Repository, WWARN will standardise data sets according to the WWARN Clinical Data Management and Statistical Analysis Plan and pool all primary data sets into a single database of quality-assured individual patient data. 

The presence of gastrointestinal drug tolerability, haemolysis and anaemia will be assessed according to the effect of daily primaquine mg/kg dose. Univariable and multivariable logistic regression analyses will be undertaken where possible. The effect of total primaquine mg/kg dose and the duration of the primaquine regimen on the risk of recurrence will be explored by time to event analysis with multivariable Cox regression analysis undertaken where possible.

The Primaquine Latin American Study Group comprises participating investigators who contribute relevant data sets to the pooled analysis. Data sets will remain the property of the investigator and will not be shared without their consent. A/Prof Andre Siquiera, Prof Marcus Lacerda, Prof Anielle de Pina-Costa, Dr Megha Rajasekhar, Ms Kathy Nguyen, Prof Ric Price and A/Prof Rob Commons will oversee the statistical analyses. The Study Group will assign a Writing Committee to coordinate activities including data analysis and drafting of publications and reports for complete group review. The Writing Committee will comprise A/Prof Andre Siqueira, Prof Marcus Lacerda, Prof Anielle de Pina-Costa, A/Prof Rob Commons, Prof Ric Price and other interested investigators undertaking the data analysis and preparation of the manuscript. Authors will be recognised according to the ICMJE guidelines and the WWARN publication policy.

For further information, please contact Rob Commons on email: rob.commons@wwarn.org