The Fight Against Malaria. Chronicles From the Laboratory

Malaria is, without any doubt, the most significant parasitic disease in humans. Almost half of the world’s population lives at risk of infection in areas where the disease is endemic. According to recent data from the World Health Organisation (WHO), in 2015 there were over 200 million cases of malaria worldwide and the disease caused more than 400,000 deaths, mostly affecting children under five years of age in sub-Saharan Africa.

Malaria primarily affects the world’s most vulnerable countries, thus reinforcing the poverty cycle

A map showing the distribution of the areas where malaria is endemic reveals that the disease primarily affects the world’s most vulnerable countries, the places with the most fragile health systems and the least investment in scientific research, thus reinforcing the poverty cycle. Despite the terrible impact revealed by the WHO figures, efforts between 2010 and 2015 in countries where malaria is endemic—supported by the international community—succeeded in reducing the number of cases by 20% and the number of deaths caused by the disease by one third. If we look at the last 15 years, the reduction in the burden of the disease is much greater. However, the emergence of parasites resistant to artemisinin (currently the main treatment for malaria) and the increased resistance among Anopheles mosquitoes to pyrethroid insecticides are two factors that represent a serious threat to the progress achieved in recent years.

Malaria cannot be completely eliminated from the planet with the control methods and treatments available to us today

Most of the scientific community accepts that, quite possibly, malaria cannot be completely eliminated from the planet with the control methods and treatments available to us today. The recent approval by the European Medicines Agency of the first RTS,S malaria vaccine (Mosquirix^TM) is a great advance given the high mortality we are talking about; however, the overall effect of the vaccine may be limited by its moderate effectiveness.

New and better tools are needed to envisage the elimination of the disease

New and better tools are needed to envisage the elimination of the disease, and to develop such tools we need a better and more complete understanding of the biology and biochemistry of the parasite, of its interactions with the host and vector and their defences against it, together with a long list of other aspects, including the need to improve the detection of asymptomatic carriers who can contribute to the spread of the disease. To bridge these known gaps in our knowledge—what we know we do not know—we have to redouble our efforts to investigate many known aspects of the disease. And, as scientists, we must also take into account the unknowns, in other words what we do not know we do not know, the new discoveries and unexpected findings—often generated by basic research—that may have an even greater impact than targeted research.

Basic research can lead to the development of new and much needed tools for the fight against malaria

To cite just one example of how basic research can lead to the development of new and much needed tools for the fight against malaria, and also to illustrate how long this process can take, we can point to two papers recently published in The Lancet Infectious Diseases reporting on clinical trials of DSM265, a new drug for the treatment and prevention of malaria. While DSM265 has demonstrated only moderate potency in stopping the growth of the parasite, the fact that the drug remains for a longer time in the patient’s bloodstream could open the door to the possibility of a single-dose cure and makes it a promising combination partner for other existing medicines. The drug targets dihydroorotate dehydrogenase, an enzyme essential for the parasite metabolism described in a study published in 2002, which detailed the function of the enzyme and its potential as a therapeutic target.

Obviously, the vast majority of studies will not be so fruitful and will never lead to the development of more effective anti-malarial drugs or interventions. However, we can be certain that, without this kind of research, it will be extremely difficult to develop the tools required to eliminate malaria.