Tafenoquine is an investigational medicine that has completed phase III studies. If approved, it would be the first new medicine for relapsing malaria in over 60 years. Tafenoquine will potentially offer a single-dose cure for the liver-stage of P. vivax infections and will be administered alongside a standard 3-day chloroquine or potentially an ACT treatment regimen.
Tafenoquine is a member of the same chemical family as primaquine; both are associated with a risk of haemolytic side-effects in a subset of patients lacking adequate levels of the enzyme glucose-6-phosphate dehydrogenase (G6PD) (on average 8% of people in malaria-endemic countries).1 To reduce the risk of haemolysis, GSK is working with PATH on the development of a quantitative G6PD point-of-care diagnostic test so that patients’ G6PD status can be tested to determine if tafenoquine or primaquine can be safely administered. The goal is for this field-ready diagnostic test to be available at the same time as the potential launch of tafenoquine in malaria-endemic countries.
Dr Marcus Lacerda has been treating malaria patients in the Amazon since 2000 and was a Principal Investigator for the phase III efficacy trial of tafenoquine in Manaus. He talks about managing malaria in the Amazon and how tafenoquine, if approved, could help.
1. What are the biggest challenges in the management and treatment of malaria in the Amazon today?
P. vivax is the big challenge. In Brazil, over the last 20 years the burden of reported malaria cases caused by Plasmodium falciparum has come down from 50% to 10−15%.2 The story is very similar across Latin America. As P. vivax doesn’t kill as many people as P. falciparum, policy-makers are shifting their attention to other diseases such as Zika and becoming less concerned about malaria. This is a problem because P. vivax, which now causes 80−85% of cases, can also be lethal. It also contributes significantly to morbidity and has a substantial economic impact.
In addition we have only one treatment to prevent relapses − primaquine − which in Brazil is administered twice daily for at least 7 days. For various reasons, including poor compliance to treatment, primaquine only works for three out of four people (determined at 6 months’ follow-up). It’s very tough to explain to patients why they should take 7 days of pills to treat something that appears to have resolved after the third day.
2. What role could a new medicine like tafenoquine play in this context?
Three years ago a plan to eliminate P. falciparum malaria in Brazil was released. This was triggered by emerging drug resistance in south-east Asia. But no one has ever considered a P. vivax malaria elimination plan because we simply don’t have the tools to address it at the moment. If approved, tafenoquine could potentially change that.
3. What proportion of people in Brazil have G6PD deficiency?
It depends on the immigration profile. Most published papers on the subject say the average prevalence among men in Brazil is around 5%. In areas where you have more people of African descent, however, the frequency can reach 20−25%.
The Ministry of Health is currently supporting a large survey of the prevalence of G6PD deficiency in the whole population of the Brazilian Amazon and so far, preliminary results confirm it’s around 5%.
4. What is the status of G6PD testing in Brazil today?
At the moment patients are not routinely screened for their G6PD deficiency status before they receive primaquine. In fact, nowhere in Latin America does this routinely happen. In some reference centres in Brazil, we have tests which are performed to diagnose deficiency among those who have already haemolysed to help understand why. I would, however, like to see this change and for G6PD testing to become routine.
5. Do you foresee any challenges to the combined implementation of tafenoquine and a G6PD test?
While the situation today is still hypothetical, what we do know is that testing is clearly more cost-effective when compared with hospitalizing people with severe haemolysis.
If tafenoquine becomes available it could potentially improve case management of P. vivax patients and push G6PD testing forward. There will of course be challenges, for example, as the degree of G6PD deficiency varies among patients, we will need to determine the cut-off for when people will be able to receive tafenoquine and when they won’t. Through addressing these challenges we will learn a lot, ultimately, for the benefit of patients.
- Howes RE et al. “G6PD deficiency prevalence and estimates of affected populations in malaria endemic countries: a geostatistical modelbased map.” PLoS Med. 9(11):e1001339 (2012).
- Siqueira AM et al. “Plasmodium vivax Landscape in Brazil: Scenario and Challenges.” Am J Trop Med Hyg. 95(6 Suppl):87-96 (2016).