New opportunities to prevent P. vivax malaria relapse
According to an article from the World Health Organisation, more than one-third of the world’s population is at risk of Plasmodium vivax (P. vivax) malaria, the second most common species of malaria. The WHO World malaria report 2018 indicates that the P. vivax parasite accounted for an estimated 7.4 million cases of malaria worldwide in 2017. About 82% of P. vivax malaria cases in 2017 are found in just 5 countries: Afghanistan, Ethiopia, India, Indonesia and Pakistan.
For the treatment of P. vivax malaria, WHO recommends standard antimalarial medicines followed by a 14-day regimen of primaquine to prevent relapses of the disease. Though primaquine is highly effective, patients are required to take daily doses of the medicine for a full 2-week period. As such, treatment compliance is a challenge.
A new medicine, tafenoquine, offers fresh hope in global efforts to combat P. vivax malaria. Tafenoquine has the distinct advantage of being a single-dose treatment, thereby increasing the likelihood of treatment compliance. It was recently approved by 2 stringent regulatory agencies, the United States Food and Drug Administration and the Australian Therapeutic Goods Administration for adults 16 years of age and older.
A key safety challenge
There is, however, a key safety challenge associated with both tafenoquine and primaquine. Among patients who have a deficiency of the enzyme G6PD (glucose-6 phosphate dehydrogenase) – a genetic condition with a prevalence of up to 35% in some countries affected by P. vivax malaria – the drugs can trigger a severe blood disorder known as acute haemolytic anaemia.
Knowing an individual’s G6PD status before treatment is critical to mitigate the risk of patient harm. This is particularly important for tafenoquine as it is a single-dose treatment and the drug remains in the blood for several days; as a result, haemolysis could continue for days in patients with G6PD deficiency. Primaquine, which is eliminated in a matter of hours, can be stopped if symptoms and signs of haemolysis occur.
For tafenoquine, a precise measurement of G6PD status (quantitative) is required. At present, quantitative G6PD tests are only accessible in well-resourced laboratory settings; such tests are not readily available for many people living in countries affected by P. vivax malaria. To safeguard the health of these vulnerable populations, the introduction of tafenoquine should be accompanied by a WHO prequalified point-of-care quantitative G6PD test.
Several point-of-care quantitative G6PD tests are either under development or have recently entered the market; some are expected to be submitted by manufacturers for review by WHO’s prequalification team in late 2019. The WHO prequalification process aims to ensure that in vitro diagnostics, medicines and other health products meet global standards of quality, safety and performance.
WHO guidance around the use of tafenoquine for the treatment of P. vivax malaria will be developed in parallel with a review of G6PD point-of-care quantitative tests. The guidance will be developed in an independent, comprehensive and efficient manner through a collaborative process that involves the 3 levels of the Organization