Reducing the risk of P. vivax after falciparum infections in co-endemic areas - a randomized controlled trial (PRIMA)
 

Aim:

To simplify malaria treatment in co-endemic areas, by assessing the use of primaquine radical cure in Plasmodium falciparum patients to reduce the risk of subsequent P. vivax.

Rationale:

In the Asia Pacific, National Malaria Control Programs repeatedly call for better approaches for radical cure, to meet their malaria elimination targets¹. 

In the Asia Pacific region, the Horn of Africa and Americas, malaria is mostly caused by two species Plasmodium falciparum and P. vivax. Unlike P. falciparum, P. vivax forms dormant liver stages that reactivate weeks or months following an acute infection causing active disease. The WHO currently recommends a treatment with primaquine to kill the liver stage parasites, referred to as radical cure. But this is only indicated in patients presenting with P. vivax malaria. However recent evidence^2,3 suggests that the risk of relapsing P. vivax malaria is higher after an acute P. falciparum infection than the natural relapse rate or the rate of reinfection would suggest. This suggests that in some locations a universal policy of primaquine radical cure for both falciparum and vivax malaria maybe warranted

To explore this strategy, we are conducting a randomised controlled trial to assess the safety and efficacy of primaquine treatment in patients with P. falciparum to reduce the risk of subsequent P. vivax episodes.

Implications for policy and practice:

Recurrent episodes of P. vivax put a strain on healthcare systems. A unified treatment policy for malaria might confer significant individual, public health and operational benefits in regions co-endemic for P. falciparum and P. vivax. The optimal use of limited financial resources could necessitate strategies for treating P. vivax through universal radical cure.

Our research locations:

• Bangladesh
• Ethiopia
• Indonesia

Study title:

Reducing the risk of P. vivax after falciparum infections in co-endemic areas - a randomized controlled trial (PRIMA).

Study purpose:

• To compare the safety and efficacy of a high dose primaquine treatment in G6PD normal patients with P. falciparum to reduce the risk of subsequent P. vivax episodes to current standard practice.

Objectives:

Primary

• To assess the safety and efficacy of a 7-day course of high dose primaquine treatment regimen in preventing recurrent symptomatic P. vivax parasitaemia in G6PD normal patients following uncomplicated P. falciparum malaria.

Secondary

• To assess the efficacy of a 7-day course of high dose primaquine treatment regimen in preventing recurrent symptomatic and asymptomatic P. vivax and P. falciparum parasitaemia
• To assess the relationship between Hb and G6PD activity over time

For more information visit the clinical trials website.  

Project dates:

The trial is complete. 

Project team:

Chief investigator:

• Dr Kamala Ley-Thriemer

Project manager:

• Contact Hellen Mnjala for further information about the study.

Investigators:

• Dr Benedikt Ley – Menzies School of Health Research
• Professor Ric Price -Menzies School of Health Research
• Professor Asrat Hailu – Addis Abeba University, Ethiopia
• Dr Tamiru Degaga -ArbaMinch University, Ethiopia
• Dr Shafiul Alam –icddr,b, Bangladesh
• Dr Wasif Ali Khan – icddr,b, Bangladesh
• Professor Inge Sutanto- Faculty of Medicine Universitas, Indonesia
• Professor Kevin Baird- Eijkman-Oxford Clinical Research Unit (EOCRU), Indonesia

Collaborators:

• icddr,b
• Eijkman Oxford Clinical Research Unit
• Addis Ababa University
• Arba Minch University.

Funders:

• Australian Academy of Science
  • The funding is provided by the Australian Academy of Science, on behalf of the Department of Industry, Innovation and Science. The Regional Collaborations Programme is supported by the Australian Government under the National Innovation and Science Agenda.
     
• Bill and Melinda Gates Foundation.

Photo credits:

• Pearl Gan in association with OUCRU, Vietnam and EOCRU, Indonesia.

Study protocol

• Thriemer, K., Degaga, T. S., Christian, M., Alam, M. S., Ley, B., Hossain, M. S., Kibria, M. G., Tego, T. T., Abate, D. T., Weston, S., Karahalios, A., Rajasekhar, M., Simpson, J. A., Rumaseb, A., Mnjala, H., Lee, G., Anose, R. T., Kidane, F. G., Woyessa, A., Baird, K., … Price, R. N. (2022). Reducing the risk of Plasmodium vivax after falciparum infections in co-endemic areas-a randomized controlled trial (PRIMA). Trials, 23(1), 416. https://doi.org/10.1186/s13063-022-06364-z