From genome data to malaria control

Genomic surveillance of malaria is vital in the fight to control and eliminate it. As is the case for COVID-19, it can be used to identify new variants, track the spread of strains of the pathogen in space and time, and pick up emerging resistance to drugs, diagnostic tests and vaccines

An essential part of MalariaGEN’s work is sequencing the DNA of Plasmodium parasites that cause malaria, which is done using several methods. Firstly, whole genome sequencing, with the resulting data being used for research to understand which parts of the genetic code are playing a role in the parasites’ biology. The knowledge is also used to inform the amplicon sequencing, a second approach and a key tool for MalariaGEN.

Amplicon sequencing focuses on specific regions of interest within the genome – for example the regions linked to drug and insecticide resistance. This means it is faster and simpler than whole genome sequencing. It also allows samples to be pooled together for analysis, so they can be used to detect emerging variants.

Georgia Whitton is a data scientist in the MalariaGEN team at the Sanger Institute, working on amplicon sequencing.

“Amplicon sequencing can be used to tell us about the species present, genetic diversity and any potential drug resistance - we can target all these areas in the parasite genome.”

“We are guided by our partners across the globe in terms of what to look for, what the metrics should be, and what the priorities are. We aim to deliver a report that covers everything important in terms of applying genomic knowledge to malaria control programs. We're making use of the sequence data,” Georgia says.

Georgia says the best part of her role is being so close to the people who use the data. “I’m not just writing code and putting it on the internet. I’m helping someone have better products, and helping them to make more informed decisions about malaria control in their country,” she says.

Dr Richard Pearson is also a data scientist in the MalariaGEN team, though working on the whole genome sequence data.

“Malaria genome data are used to inform the development and use of vaccines, treatments and diagnostics,” he says.

Malaria parasites have evolved resistance to treatments over the years, including most recently, multidrug resistance to first-line treatments. This was first seen in South East Asia and reported in 2018, where a single multidrug resistant strain of the Plasmodium parasite emerged and spread aggressively. The strain outcompeted all of the other resistant malaria parasites, leading to complete failure of treatment in Cambodia.

There have been recent reports of parasites in Africa showing similar drug resistance¹. At the moment, treatments are not failing in the clinic, and the signs of resistance are only seen in the parasites' genomes. It appears this has evolved independently to the drug resistance seen in South East Asia².

“This is a very key thing to watch, to see if this drug resistance is increasing in Africa, or in any region. This information is vital for national malaria control programmes, helping to inform treatment choice, for example,” says Richard.

In terms of diagnosis, there are also signs that malaria parasites are evolving to evade the current standard test. The test works much like a COVID-19 lateral flow test, and picks up a particular protein in the parasite. Many strains of plasmoduim have deleted the genes that code for this protein from their genome, and so go undetected and then could therefore remain untreated, and continue to spread³.

The first ever malaria vaccine was introduced last year, and as for COVID-19, genome data are going to be vital to monitor for any potential immune escape. “Our sampling strategy, and our collaborations, are going to be key as we move forward,” says Richard. “This will help us collect the data we need to monitor the effects of interventions – be that treatments or vaccines - on parasite populations.”

Nurse does a quick malaria test from blood, South Africa

Other parallels between malaria and COVID-19 have emerged, and many of the team have been seconded to work on genomic surveillance of SARS-CoV-2 over the last two years.

“The rapid turnaround times we saw with COVID-19 genomic surveillance – that’s something we can achieve for malaria too,” says Georgia.

All of MalariaGEN’s data are openly and freely published, driven by the collective goal to advance research into the complex biology of Plasmodium species, and to accelerate genomic surveillance for malaria control and elimination.

The next steps for MalariaGEN are to help partners build sequencing and analysis capacity around the world, to continue the vital work of genomic surveillance.

To find out more visit the MalariaGEN website.