Keeping an eye on relapsing malaria

2019
Dr Kamini Mendis, Independent Consultant in Malaria and Tropical Medicine, Sri Lanka

Historically, global efforts to tackle malaria have focused primarily on Plasmodium falciparum malaria, due to its higher disease burden and associated health risks, including death – particularly among children. Conversely, Plasmodium vivax malaria is often neglected, despite having the widest geographical distribution of the five species of the parasite affecting humans. 

Dr Kamini Mendis, Independent Consultant in Malaria and Tropical Medicine, Sri Lanka, explains the successes and challenges on the road to eliminating malaria in Southeast Asia as well as the role of new tools in revitalizing efforts against P. vivax malaria.

1. Sri Lanka has successfully eliminated malaria. To what would you attribute this success?

Several factors, I would say. A key element was the leadership of the central anti-malaria campaign, which was complemented by a very effective team of regional malaria officers. Before and throughout the elimination phase, the country made sure that sound policies, effective implementation and coordination measures, as well as quality products and services, were in place to maximize the chance of success. 

A rigorous monitoring and evaluation approach was also applied to the management of grants. Sri Lanka received grants from The Global Fund for its malaria elimination efforts, and I believe it was the ability to direct these funds where needed that made the difference, probably as much as the actual funding itself. 

2. In South East Asia, P. vivax accounts for an increasing proportion of malaria cases. What do you see as the key challenges to the control and elimination of P. vivax?

One key challenge is preventing relapses. The current anti-relapse medication is primaquine (PQ), a 14-day treatment course that can only be given after testing for glucose-6-phosphate dehydrogenase (G6PD) activity because the drug can induce acute, life- threatening haemolysis in people deficient in this enzyme. In an ideal world, the G6PD status of every individual would be available as part of routine clinical testing. However, until that becomes a reality, we need a reliable quantitative test for G6PD activity that can be used at the point of care in areas where G6PD deficiency is prevalent. Unfortunately, such testing is not yet available. 

Another important challenge is correctly diagnosing P. vivax, particularly in settings where microscopy is not readily available. To enable earlier diagnosis and treatment, rapid diagnostic tests for P. vivax that are at least as sensitive as those for P. falciparum are urgently needed. 

The final challenge is blocking transmission. In parts of Asia where malaria persists today, transmission occurs in and near forests, where mosquitoes bite and stay outdoors. As such, they are not very amenable to house-spraying with insecticides or to the use of insecticide-treated bed nets, making it very difficult to control the vector. 

Despite these challenges, several countries have either already eliminated, or are moving towards, eliminating P. vivax malaria, which shows that the tools we already have at our disposal can in fact not only control, but eliminate, the disease.

3. Do you think that the new tools could revitalize efforts to control P. vivax malaria?

Yes, I do. If we could achieve radical cure in every patient with P. vivax, it would have a huge impact on transmission. This is because relapses, which account for a large proportion of infections, contribute substantially to the human reservoir of infectious parasites. Tafenoquine (TQ) is a newly approved single-dose radical cure that, in combination with G6PD testing, could help to deplete this reservoir. The challenge is translating this efficacious combination of interventions into a workable practical approach.

Safety is probably the single most important consideration with TQ. Even with a highly accurate test for G6PD activity, the safety of TQ depends on our ability to use it correctly. It is difficult to predict how (whether) and at what level of the healthcare system we can entrust healthworkers to use the test reliably, and to what extent countries will actually adopt and use the system. Any actual, or even perceived, adverse event related to improper use or interpretation of the G6PD test could seriously jeopardize its uptake.

4. What needs to be done to support the use of a G6PD quantitative test plus TQ or PQ within malaria control programmes?

The only way of knowing if the use of G6PD testing plus TQ or PQ is well tolerated and effective in practice is to carry out feasibility studies in a range of endemic countries that already have safety precautions in place. These experiences could then inform decisions about where in the health system these tools could be safely introduced.