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G6PD testing for improved radical cure of P. vivax malaria

What is this project?

Our focus is to support access to new G6PD diagnostics for the safe administration of Plasmodium vivax radical cure, to prevent clinical relapses and help eliminate P. vivax malaria. FIND is generating evidence to facilitate the implementation of G6PD testing at the point-of-care. This includes the cost-effectiveness of different G6PD testing strategies, lessons learnt from training workshops with a quantitative hand-held G6PD diagnostic, a social science study on the barriers to G6PD testing, and an inter-laboratory reproducibility assessment of a quantitative G6PD test.

 

Why are we working on it?

People with reduced activity levels of the metabolic enzyme glucose-6-phosphate dehydrogenase (G6PD) are at high risk of hemolysis when treated with 8-aminoquinolines, currently the only available drugs to treat P. vivax parasites during the dormant liver stages of their life cycle. More than 400 million people worldwide have some level of G6PD deficiency, which is especially common in malaria-endemic regions. Best clinical practice requires G6PD screening before administering these antimalarial drugs, yet few tests meet the technical requirements for use in the settings where most P. vivax patients seek treatment. Access to G6PD testing and effective treatment is therefore currently limited and progress towards P. vivax elimination is slow. However, new G6PD diagnostics are coming to the market and evidence is needed to support their implementation.

Quantitative G6PD diagnostics currently represent the safest option for ensuring access to efficient P. vivax radical cure. A relatively simple, hand-held quantitative G6PD test, the STANDARD™ G6PD test (“G6PD biosensor”), has been developed by SD Biosensor and PATH but more evidence is needed on the feasibility of implementing it in routine practice and to define the most efficient testing strategies.

 

What does it involve?

The project encompasses four main activities:

1. Compare the cost-effectiveness of different G6PD testing and treatment strategies
A cost-effectiveness analysis was conducted to compare different P. vivax case management strategies. The analysis combined qualitative or quantitative G6PD testing with different options for radical cure (single dose, short course or long course regimens) in four endemic country settings where G6PD testing is not currently routine. The impact of each strategy on DALYs (disability-adjusted life years) and costs was compared with current case management in each country. Results indicate that introducing G6PD screening will not only contribute to reducing disease burden but that it is, in certain settings, cost-effective over the current care for P. vivax patients.

2. Develop and evaluate training tools for a quantitative G6PD biosensor:
A training workshop on the theoretical and practical aspects of G6PD testing was conducted with medical technologist health workers (HWs) from primary level health care facilities in Bangladesh in 2019.  This was followed by a practical session with the G6PD biosensor and a proficiency assessment. The training tools and materials used during this workshop were developed by PATH and FIND and were found to be effective for training on the correct use of the G6PD biosensor. They are available here:

This work has been presented in a webinar organized by the G6PD Operational Research Community of Practice (GORCoP), available here.

3. Determine barriers and facilitating factors for the implementation of the G6PD biosensor:
The training also included focus group discussions (FGDs) led by social scientists to get feedback on the ease of use and feasibility of implementing the G6PD biosensor. Individual interviews with some HWs as well as public health officials were also conducted. This work provided useful insights into different issues to consider, such as the health system level to target for testing and the perceived value of testing in settings with falling malaria cases. The FGDs and interview questionnaires are made available here, and a full analysis has been published:

This work has also been presented in a GORCoP webinar and published in the Malaria Journal.

4. Assessing the reproducibility of a quantitative G6PD biosensor: a diagnostic compatible with universal thresholds for guiding safe treatment?
Quantitative G6PD diagnosis requires cut-off thresholds to inform P. vivax treatment decisions. Current reference methods show significant inter-laboratory variability in results, meaning that lab-specific thresholds must first be established through bespoke local population surveys. To investigate whether this barrier to implementation can be avoided with the new quantitative G6PD diagnostics, a reproducibility assessment of the STANDARD G6PD test (SD Biosensor, Rep. of Korea) was conducted across 10 sites to assess inter-laboratory variability. G6PD results did not differ significantly between sites and users. If further studies under field conditions generate comparable results, the biosensor would allow standardized cut-offs for G6PD activity levels to be defined. This would greatly simplify the roll out of novel highly effective radical cure treatment regimens for P. vivax infections. A full overview of the study findings has been published in PLoS Neglected Tropical Diseases.

 

What do we expect to achieve?

New point-of-care diagnostic tools for G6PD testing have become available but are not yet widely used. Through the targeted activities described above, FIND aims to contribute to improving access to these new tests and generating evidence to accelerate their roll-out. Ultimately, this will allow wider and safer implementation of P. vivax radical cure, reduce the burden of relapse infections, and contribute to the elimination of P. vivax malaria.

 

Partners and funding

The project is being carried out with our partners at the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b, activities 2, 3 and 4), Menzies School of Health Research (Menzies, all four activities), and Maastricht University (UM, activity 3). Colleagues at PATH are also acknowledged for their support to the project.

This body of work is funded by the government of Australia.