PATH Case Study

G6PD diagnostics: Improving health outcomes and breaking the cycle of malaria transmission

December 12, 2022

Simple, affordable, and robust point-of-care diagnostics for G6PD deficiency, a common hereditary condition, are critical to supporting curative treatment for P. vivax malaria and accelerating elimination.

Challenge

G6PD diagnostics are needed to support equitable access to treatment for P. vivax malaria and reduce the global burden.

Solution

PATH, SD Biosensor, and partners developed and commercialized G6PD diagnostics to expand equitable access to radical cure.

Location

Brazil, Cambodia, Ethiopia, India, Laos, Peru, Myanmar, Vietnam

Partners

See the partners and donors listed below.

Path Expertise Areas

Product development

Clinical Validation

Operations research

Quality assurance

Regulatory submissions

Human-centered design

The Challenge

Summary

P. vivax is the most challenging type of malaria to treat and eliminate because a form of the parasite (hypnozoite) can lie dormant in the liver, causing recurring malaria and infectivity even after treatment with typical antimalarial drugs.
Curing a patient requires using 8-aminoquinoline drugs, such as primaquine and tafenoquine, to kill the parasites in the liver.
Patients deficient in glucose-6-phosphate dehydrogenase (G6PD), a common enzyme deficiency, are at risk of adverse effects such as hemolytic anemia when treated with these drugs.
The World Health Organization recommends testing patients for G6PD deficiency before receiving radical cure treatment.
However, simple point-of-care tests for G6PD deficiency that can be used by community health workers in rural areas where malaria patients typically live are simply not available.
This poses a major challenge to P. vivax malaria control and elimination efforts.

The challenge

Up to 2.85 billion people may be at risk of infection with Plasmodium vivax (P. vivax), a form of malaria found in Asia, Latin America, and the horn of Africa. Also known as recurring malaria, P. vivax causes an estimated 6.4 million malaria cases per annum and represents a key obstacle to global efforts to control or eliminate malaria. P. vivax is a challenging type of malaria to treat because a form of the parasite known as the hypnozoite can lie dormant in the liver and cause recurring illness weeks or months after the first infection. P. vivax is also hard to eliminate because, during relapse, the patient becomes infectious, perpetuating the transmission cycle of P. vivax in the community.

Typical malaria treatments will kill the forms of the parasite in the bloodstream but do not kill the hypnozoites in the liver. When all forms of the parasite, including hypnozoites, are killed to completely cure a patient with P. vivax, it is known as “radical cure.” Radical cure is essential to stopping the spread of the disease. Currently, radical cure for P. vivax can be achieved only through treatment with 8-aminoquinoline-based drugs such as primaquine and tafenoquine. However, patients deficient in glucose-6-phosphate dehydrogenase (G6PD), an enzyme that helps protect red blood cells from oxidative damage, are at risk of hemolytic anemia, or even death, when treated with these drugs.

Due to the risk of hemolytic anemia, patients with severe G6PD deficiency should not receive the standard course of primaquine or tafenoquine for radical cure of P. vivax. Because females can carry the gene that causes G6PD deficiency on one or both X chromosomes (known as heterozygosity), these females can have varying levels of G6PD activity, which makes that particularly hard to diagnose.

It is estimated that 400 million people worldwide are G6PD deficient, which is common in areas where malaria is endemic. The World Health Organization and clinical best practices recommend testing patients for G6PD deficiency before treating them with an 8-aminoquinoline-based drug. However, simple and effective tests for G6PD deficiency are not widely available at the point of care (POC). A reliable and accurate POC diagnostic for G6PD deficiency is needed to enable wide-scale radical cure treatment of patients with P. vivax malaria and accelerate the elimination of the disease.

The approach

Early market landscaping in 2011 identified challenges to ensuring the availability of a high-quality point-of-care test for G6PD deficiency, which included small market size, the technical difficulty of product development, and the minimal regulation of products already in the market.

This informed a decision to invest in a portfolio of G6PD diagnostic test candidates to ensure the availability of at least one test that could be used at the point of care for malaria treatment. It also informed the decision to create a product development partnership, which brings together public, private, academic, and philanthropic expertise and funding to develop and deliver global health products that would otherwise have little or no chance of coming to market.

Learn more about PATH’s G6PD Diagnostic Initiative product development partnership.

The solution

PATH partnered with multiple diagnostic developers to advance point-of-care tests that could be used by health care providers in low-resource settings to identify G6PD-deficient patients. This would ensure the availability of affordable and appropriate G6PD testing options that best meet the needs of health care providers managing malaria cases.

By the end of 2014, the product development partnership advanced the early-stage development of three G6PD diagnostic tests. In 2016, two tests transitioned into the product development and validation phases, but a new quantitative G6PD test already in development by a Korea-based diagnostics company, SD BIOSENSOR, soon emerged as a leading candidate.

With technical support to improve performance to meet PATH target product profile standards, market intelligence, and access to samples in PATH’s G6PD repository, SD BIOSENSOR accelerated the progress of its G6PD test while also reducing the costs associated with clinical validation and generating data for regulatory submissions.

Partnering with the Vietnam National Institute of Malariology, Parasitology and Entomology to conduct training for an operations research study on point-of-care G6PD testing. Photo: PATH/Spike Nowak.

The impact

In 2017, the STANDARD™ G6PD Test from SD BIOSENSOR was registered in India and Thailand, becoming the first quantitative G6PD point-of-care test available in a malaria-endemic country. With PATH support, the company completed clinical evaluations to obtain regulatory approval and register its test in high-priority countries. Upon receiving approval from the Expert Review Panel for Diagnostics in 2019, procurement agencies, including the Global Fund, were able to order and distribute tests to additional P. vivax malaria-endemic countries.

In 2021, the STANDARD G6PD Test received approval from the Australian Therapeutic Goods Administration, assuring its quality and efficacy and confirming its suitability for use in low- and middle-income countries. At this time, it was registered in 18 malaria-endemic countries, improving P. vivax case management and supporting the reduction in the global malaria burden. In 2022, Cambodia, Laos, and Vietnam introduced routine test use with primaquine (the standard treatment for P. vivax). In Cambodia, the STANDARD G6PD Test has enabled equal access to radical cure of P. vivax malaria for males and females for the first time. In Brazil, to date, more than 1,600 P. vivax patients have been tested with the STANDARD G6PD Test and treated with single-dose tafenoquine. It is currently the only quantitative POC G6PD test commercially available to support the introduction and use of tafenoquine, and it is distributed to over 30 countries. The test allows equitable access to the same standard of care for both men and women.

PATH continues to work with manufacturers, governments, malaria-endemic country partners, and regulatory bodies to increase access to POC diagnostics and integrate them into national malaria case management practices. PATH has created training materials and quality assurance tools to support G6PD testing while also leading an operations research community of practice for global G6PD diagnostics researchers and end users to accelerate the introduction and scale-up of new tests. In September 2022, MedAccess, SD BIOSENSOR, and PATH announced a partnership to secure the supply of the STANDARD G6PD Test for the next four years, ensuring availability.

PATH continues to work with P. vivax malaria countries to introduce and increase access to G6PD testing and uptake of radical cure treatment.

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