Malaria is a globally important parasitic infectious disease transmitted between humans by mosquitoes.
In 2016, 216 million people worldwide were infected and over 400,000 people died from malaria, around 90% of whom were in sub-Saharan Africa; that’s one death every two minutes. This is a tragedy for a disease which is largely treatable.
Eliminating malaria is an international priority which doesn’t just save lives but contributes to key global Sustainable Development Goals.
The challenge of controlling malaria
Malaria is transmitted between humans by mosquitoes. Although there are five species of malaria that infect humans, most human disease is caused by just two, Plasmodium vivax and P. falciparum. Together they account for over 400,000 deaths every year, ninety per cent of which occur in Africa.
Significant international effort over the last 20 years means that this number is now around half of what it was in the year 2000. Although malaria transmission is influenced by a number of factors, including climate and land use, it is likely that the main contributors to recent reductions in transmission have been human interventions: the widespread use of insecticide treated bednets, which stop infected mosquitoes from biting people and therefore infecting them, and the better use of drugs to treat disease. It is with renewed confidence then, that the global community has articulated a grand plan to eradicate malaria by 2040.
However, there are at least two important sets of challenges to this ambitious proposal. Firstly, the fight against malaria is being prolonged by a lack of sustained financial and political commitment and regional collaboration at the highest levels. Recent progress is fragile and dependent upon continued funding into the generation and application of interventions at scale. The last thing that the global fight against malaria needs now is complacency lest it become a victim of its own recent, yet historically modest, success.
The second set of challenges relate to the biology of malaria. Just as we are starting to make real gains, the parasite is beginning to fight back, and progress is in danger of being reversed because the parasite is evolving resistance to our drugs and this resistance is spreading. Therefore a crucial part of the global strategy for malaria control is to monitor the spread of antimalarial drug resistance, and identify and contain drug resistant strains when they’re found.
On top of this, the dynamics of malaria transmission are complex. For example, as parasite prevalence drops, fewer people are infected, which is clearly a good thing. However, this reduction in malaria endemicity (disease intensity) alters the rules of engagement between people and parasite. In the most endemic settings, many people will be infected by parasites, leading to high levels of asymptomatic infection due to the acquisition of functional immunity that comes from frequent exposure to the parasite. But as endemicity drops, by definition the number of people infected drops which leads to lower levels of natural immunity. Both the spread of drug-resistant infections in endemic regions, and the dynamics of infection in low endemicity settings, can therefore behave more like a disease outbreak.
The case for surveillance
So, to control and eventually eliminate malaria we need to continue to push for financial and political action and develop innovative ways of monitoring parasite and mosquito populations. We need to be able to assess levels of antimalarial drug and insecticide resistance, to understand where resistance first occurs and how it spreads, and to identify how interventions are affecting populations. What we need, in other words, is some sort of surveillance system.
A number of different types of data are currently used to understand malaria parasite and vector populations, but none has more potential for inferring key aspects of populations than genomic analysis. DNA sequencing can provide both up-to-date information about which drugs a parasite is resistant to and where a new infection comes from. This is because drug resistance is the result of mutations in the parasite genome, and by comparing an unknown parasite genome to a reference database, we can understand where it comes from.
Traditionally, genome sequencing has been expensive and lab-based, and global parasite reference datasets have been unavailable. However, recent advances in mobile genetic sequencing and the development of cloud-based genome analytics with MalariaGEN, the largest repository of parasite and mosquito sequence data in the world, mean that we now have the tools to take genetic sequencing into the field and provide the necessary information to malaria control programs, in close to real time.