Relapsing Plasmodium vivax

Prof Ric Price
2013
Prof Ric Price, Menzies School of Health Research and Charles Darwin University; and the Centre for Tropical Medicine, University of Oxford

Relapsing Plasmodium vivax malaria results in around 70–80 million clinical infections each year.1 Primaquine is the only medicine available to cure it. It has been in use for 60 years, has a very long treatment regimen and potentially fatal side effects in some patients.

Prof Ric Price discusses why P. vivax should be a research priority and what tools are needed in order to eradicate it.

1. Why do you consider P. vivax malaria to be a research priority?

P. vivax causes a huge burden globally, and outside Africa accounts for almost 40% of the world’s malaria. In some communities, young children have bouts of P. vivax every 3 to 4 weeks leading to a huge burden of disease in individuals, families and communities. As P. falciparum malaria declines, there has been a rise in the proportion of malaria attributable to P. vivax, both relative and, at times, absolute. In many regions, P. vivax is now the predominant species; its ability to relapse from dormant liver stages makes it is much harder to eliminate.

P. vivax is associated with appreciable mortality. Fatal cases have been reported from several endemic countries. The most common clinical manifestation is severe anaemia and this is associated with additional respiratory or diarrhoeal infection. The consequences can be disastrous. What we don’t know is how many more people are dying directly from P. vivax or indirectly from co-associated morbidities.

2. What are the limitations of the current tools for the treatment and management of P. vivax malaria?

We lack a reliable treatment for P. vivax liver stages. Primaquine has been the only available radical cure of P. vivax malaria for the last 60 years. WHO recommends a 14-day course, which is difficult to deploy, often not implemented by malaria control programmes, and rarely adhered to by patients. Also, in susceptible individuals, it can cause haemolysis, making anaemia worse. Addressing this issue is perhaps the greatest challenge in the management of P. vivax.

In addition, the P. vivax parasite has become resistant to chloroquine. This was first described in Papua New Guinea in 1989, but appears to have spread across much of Asia and South America. However, chloroquine continues to be used as the first-line treatment in nearly all P. vivax endemic countries.

3. Do you believe P. vivax malaria can be eradicated?

Absolutely! It has already been eliminated in the UK, Italy, USA, Russia and many other countries. Sri Lanka is the latest country close to elimination. So we know we can tackle it, the question is how: through repeated blood stage treatment or expedite the process by reliably dealing with the hypnozoite.

4. What tools do we need to achieve P. vivax eradication?

As for any major public health campaign, health systems need to be strengthened. For malaria, the priorities are vector control and access to early diagnosis and treatment. But we desperately need a safe and reliable radical cure for P. vivax. This means either rethinking how we deploy primaquine or developing alternative options.

Exciting data, published at the end of last year, highlights the potential of tafenoquine, a drug under development with GSK and MMV, to provide radical cure with a single dose. If subsequent clinical trials can confirm its safety and comparative efficacy against current treatment options and it can be deployed widely, then it has potential to transform the management of P. vivax and become a major tool in the ultimate elimination of malaria. Like primaquine, however, the drug causes haemolysis in susceptible individuals and would need to be rolled out in conjunction with better diagnostics.

Significant resources are now being brought to bear in tackling these issues and in the coming years we hope to be able to ensure that goals for elimination and eradication include P. vivax as well as P. falciparum.

 


 

1. Mendis K et al. “The neglected burden of Plasmodium vivax malaria.” Am J Trop Med Hyg. 64 (1-2 Suppl):97-106 (2001).