Researching relapsing P. vivax malaria

Colonel Bagus Tjahjono, Indonesian Army Health Command, Jakarta

Although primaquine is the only approved medicine for radical cure of relapsing malaria, very little is known about how well it works in combination with other medicines that treat the blood-stage infection. In order to maximize its effective use until a suitable alternative can be developed, Oxford University, Eijkman Institute and MMV have joined forces to run a series of trials. The first trial compared primaquine + dihydroartemisinin-piperaquine (Eurartesim®) with primaquine + quinine and with artesunate. The next trial will look at the efficacy of primaquine + pyronaridineartesunate (Pyramax®) compared to primaquine + Eurartesim and to artesunate alone. The efficacy of OZ439 against the relapse will likely also be investigated.

1. Can P. vivax cause severe malaria and be fatal?

Recent work certainly suggests that it can be fatal. More evidence is needed, but certainly I believe the longheld consensus of the disease being benign is incorrect and probably quite dangerous to patients.

2. How is P. vivax malaria managed in Indonesia in terms of diagnosis and treatment? Is there a difference compared to P. falciparum malaria?

Most malaria in Indonesia is diagnosed based on symptoms initially and then confirmed with microscopy diagnosis. No distinction is usually made between P. falciparum and P. vivax. The treatment is DHA-PQP – the government recommended first-line treatment for uncomplicated malaria. In the cases where P. vivax malaria can be confirmed, the recommendation is to also treat with 14 days of primaquine.

3. What are the flaws in the way P. vivax malaria is currently managed in Indonesia?

One of the main issues is the lack of access to laboratory diagnosis and the lack of a rapid test to diagnose both P. vivax and P. falciparum malaria and G6PD deficiency. With improved diagnosis of G6PD deficiency we would be able to use primaquine safely and avoid using it in patients with this enzyme deficiency. The other problem is that primaquine is our only tool against relapse and we don’t fully understand it. We think the efficacy of primaquine very much depends on the partner drug used with it and this is why we are running the current trial.

4. How can you be sure that participants in the trial are suffering from a malaria relapse and not just a new malaria infection?

The participants in the trial are all soldiers who have returned with malaria from their duties in Papua Province and are treated back at the base in Lumajang, East Java. As there is very little malaria transmission in this region we can be sure that any further malarial episode is a relapse and not a completely new infection.

5. How is the trial progressing and what have you learnt about primaquine?

The trial is almost complete. Our results offer compelling evidence affirming the safety and efficacy of primaquine when used with DHA-PQP for radical cure of P. vivax malaria in eastern Indonesia. I am very pleased with these results and proud of my soldiers and commanders for their enthusiastic support.