How genomic surveillance is tackling malaria outbreaks

Often when people think of surveillance, they think about the observation of people, behaviour or symptoms, but what about surveillance at a molecular level?  

As the world fights against COVID-19, genomic surveillance has become an increasingly important tool to track pathogens and how they are evolving. And one team that is leading the world in this area is based right here at IMPACT.  

Professor Alyssa Barry is a Professor of Systems Epidemiology of Infection at IMPACT, with a Translational Genomics Hub at the Burnet Institute in Melbourne. She leads a number of international research projects that use genomic surveillance research to understand how pathogen populations spread and evolve. 

One such project is the STRIVE PNG program funded by DFAT through the Indo-Pacific Centre for Health Security. STRIVE PNG—Stronger Surveillance and Systems Support for Rapid Identification and Containment of Resurgent or Resistant Vector Borne Pathogens in Papua New Guinea—is made up of a multidisciplinary group of researchers and public health practitioners in Australia and Papua New Guinea (PNG). Their focus is to build a rapid reporting and response system for mosquito-borne infections such as malaria and dengue fever. 

Prof Barry directs the molecular monitoring stream of the program. As part of the program, the STRIVE PNG team set up a molecular hub based at the University of PNG in Port Moresby, which brings together researchers from the PNG Institute of Medical Research, University of PNG and scientists from the Central Public Health Laboratory—which is part of the PNG Ministry of Health’s Public Health Program.  

Eight sentinel sites have also been established across the country in both urban and rural settings where outbreaks are expected. At these sentinel sites, blood samples are collected from people who have presented with a fever. Those samples are sent back to the molecular hub, where scientists have set up diagnostic assays using polymerase chain reaction (PCR) to diagnose malaria and other arbovirus infections. 

“What we’re trying to do with this project is to build greater capacity to do more advanced molecular analysis to track infections and certain characteristics such as antimalarial drug resistance,” Prof Barry says. 

“There’s resistance mutations to the drug artemisinin emerging in malaria parasites in PNG, which are quite concerning. And we have to really track those rather carefully. Researchers in PNG can already detect some mutations but this can be time-consuming, however, we help them to do this more rapidly on-site and to further characterise the infections. What we’ve done in our labs at Deakin and Burnet Institute is developed some assays to do more detailed genetic characterisation of the parasite.  

“One of the assays tells us how many parasite strains people have been infected with, because people can be infected with multiple strains at the same time. We use molecular methods to look at that and we can also diagnose drug resistance to a whole panel of antimalarial drugs. 

“We know there is already a significant resistance to drugs that have been previously used in PNG. But what we’re really interested in are these artemisinin resistance mutations in malaria parasites, which seem to be emerging in PNG. We’re seeing them pop up in different places, but we’re not sure whether they’re spreading or whether the parasites are evolving resistance independently in those locations. And this is where the genomics comes in. By doing the genetic analysis, we have another set of markers that allow us to determine if these resistant parasites from different parts of the country are related or not. 

“This project is enabling us to detect and quantify these drug-resistant parasites. We can find out how many resistant strains are circulating and also characterise them genetically, to determine where they’re coming from.” 

Professor Alyssa Barry

Prof Barry says this analysis is integral in determining how best to approach an outbreak of drug-resistant malaria and contain its spread, as well as to support the control program to plan how to contain all malaria, not just the drug-resistant infections.  

“If we see the resistance markers and the parasites are related, we can say, that’s a population that’s spread from place to place. And if they’re not related, that suggests that what we’re actually seeing is resistance emerging independently in different parts of the country, so this would require a different control approach”, she says. 

Analysis solutions have now been developed so the assays can be done by scientists in the molecular hub in PNG using a portable DNA sequencing device. One analysis tool that has been developed is an easy-to-use software tool that can display relevant information such as a drug resistance profile and geographic origin.  

“That information then goes into a custom real-time integrated surveillance platform that’s being developed by other members of the STRIVE PNG team”, she says. 

“So we do all the molecular work, such as identifying how many infections have these drug resistance mutations, and then that all gets displayed on the surveillance platform, which would be used by the control program. This research is translational, building a bridge between research and the use of this information in public health.” 

Together with David Williams from the CSIRO’s Australian Centre for Disease Preparedness and researchers from James Cook University, who are arbovirus experts, Prof Barry and her team will be conducting virtual workshops with stakeholders—public health officials, research scientists and public health scientists—about the use of molecular and genomic analysis of pathogens to control infectious diseases. They will also run another more hands-on workshop with the team in the molecular hub to teach them how to run the genotyping and analysis. 

“What’s made the work successful is those really strong cross-disciplinary collaborations and the connections in malaria endemic countries such as PNG”, Prof Barry says. “Working in diverse teams is integral to tackling infectious diseases, such as malaria”. 

Prof Barry is hopeful that the systems set up through STRIVE PNG will have a long lasting effect on the country’s fight against malaria. The expertise of the STRIVE PNG molecular hub team has already proven to be highly adaptable having also been applied to tracking COVID-19 in PNG. 

 “Sustainability is key to the success of this program—to be able to see us establish that pathogen genomic surveillance capacity in PNG and it to be self-sustaining—where the scientists we train become the trainers. That’s something that is happening already,” Prof Barry says.  

“We have a Papua New Guinean PhD student and they’ll go back to PNG and start up their own lab and become a leader. So that would be the measure of real success—to see that we could sustain it beyond the life of the program.” 

In 2021, Prof Barry hopes to see the assays adapted to the portable platform and well established in PNG. 

“We have the molecular assays up and running, and we need to have the analytical tool completed and tested,” she says. “The program has been extended to 2022, so the goal for this year is to really see things transferred across to PNG and being used on the samples that are coming in on a weekly basis from the sentinel sites.”

This piece is a real world impact article that was recently published in our annual report. Read the full report here