Vivax Malaria Eradication: Where Are We Now?

The reestablishment of malaria eradication as an international goal has repositioned Plasmodium vivax on the malaria research agenda. Papers devoted to this species have more than doubled during the last decade, and over the last years, four scientific conferences have been devoted to this malaria species, the last one in May 2013, in Barcelona, Spain.

Although less lethal than malaria caused by P. falciparum, vivax malaria is far more widespread: more than 2.5 billion people live at risk of being infected by a parasite that is also responsible for severe disease, and even death, mostly in Asia and Latin America. However, there is far less research ongoing about vivax basic biology, epidemiology and intervention strategies. The ratio between P. vivax and P. falciparum publications is still 1 to 4, although this also means a significant improvement considering that it was 1 to 10 only ten years ago.

As discussed during the recent conference in Barcelona, a lingering question remains:  will P. vivax  be more difficult to eliminate than P. falciparum, as has been claimed in the past?

The question is itself most curious, since major advances have already been made against P. vivax. Most countries that have achieved malaria elimination were predominantly ‘vivax territories’, and so are most regions currently approaching this final goal. This is so despite a number of unique characteristics in the biology of P. vivax that makes its management and elimination particularly challenging.

This species is often transmitted by mosquitoes that bite outdoors and during day time, which renders traditional vector control less effective. Gametocytes develop earlier in the parasite life cycle, allowing transmission to occur before clinical symptoms are apparent. Most importantly, the vivax life cycle comprises a dormant stage that can cause relapses months and even years, following the original infection, constituting a reservoir of infection that represents the biggest hurdle for elimination and ultimately eradication  of P. vivax. 

The biological challenge that P. vivax represents is being addressed by still a very few number of scientists. However, encouraging steps are being taken to increase our understanding of hypnozoite biology, including advances in the development of in vitro/ex vivo culture systems, systems biology approaches and new tincture methodologies that might allow distinguishing between the two liver stages of this parasite life cycle: hypnozoites and hepatic schizonts.

But many questions remain unresolved. If we could – should we awaken dormant parasites, making them easier to treat? How do we assess, and minimize, the risk caused by primaquine, currently the only licensed radical cure  drug available, but which causes haemolysis in patients with severe Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

In addition to development of new, safer drugs against the dormant stages of P. vivax, other tools specifically designed for malaria eradication include vaccines capable of interrupting transmission by eliciting long lasting immune responses that prevent infection or inhibit gametocyte development, or, as showed by one of the speakers at the conference, attacking the parasite while it develops in the mosquito midgut.  There is also consensus that, as good as new tools might be, eradication will be made feasible through use of a combination of interventions, including non-technological components such as strong health and surveillance systems, sufficient funding, and political will.

The use of Mass Drug Administration for both radical cure and prophylaxis, enabling P. vivax eradication, remains a matter for debate. Would it be acceptable to administrate drugs to populations of primarily healthy people, or would we need to develop a diagnostic tool to identify hypnozoite carriers? Although there is some fear of cultural barriers for accepting what could be perceived as authoritative interventions, it is important to remember that, historically, preventive tools have been very well accepted in public health: travelers to malaria endemic areas regularly take antimalarial drugs as prophylaxis, Mass Drug Administration is a keystone of the current paradigm for neglected infectious diseases, and vaccines are used massively against diseases for which the risk is minimal as long as programs are sustained.

P. vivax has to be addressed as part of the global strategy against malaria. It co-exists with P. falciparum in large parts of the world, it causes significant disease, and its fight requires a combination of strategies. It is not surprising that it will take research translated into implementation, and the best data, to reach long term goals such as malaria eradication.

The World Health Organization is currently preparing a global strategy and operational manual against P. vivax, and this species will occupy a key position both in the forthcoming Global Technical Strategy for Malaria Control and Elimination and into the revised Global Malaria Action Plan. Furthermore, the revised Malaria Vaccine Technology roadmap will consider P. vivax as a priority for the first time.

The progress leaves the community with a sense of optimism. Investments are giving results, and P. vivax is receiving the attention it deserves. However, big challenges also lie ahead, including how to sustain investment for this species, in the context of a shrinking and increasingly competitive R&D envelope.

This post was written with the support of Pedro L. Alonso and N. Regina Rabinovich and simultaneously published on The Lancet Global Health Blog.