Genomic Surveillance Finds Malaria-Causing Parasites Resistant to Treatments

Scientists have discovered new strains of malaria-causing parasites in Ethiopia that are both resistant to current treatments and evade detection by common diagnostic tests—a development that could increase malaria cases and deaths while making eradicating the disease even more difficult.

In Nature Microbiology, the scientists described their findings from a genomic surveillance study. Scientists had already discovered strains of the parasite that cause malaria that were resistant to most existing antimalarial medications in Uganda, Tanzania, and Rwanda, and malaria parasites resistant to diagnostic testing had arisen in the Horn of Africa.

Those parasites have been spreading separately, but according to study author Jeffrey Bailey, an associate professor of translational research, pathology, and laboratory medicine at Brown University, this is the first published report that validates the widespread presence of this type of double-resistant malaria strain.

Now we are essentially seeing the worst-case scenario: parasites with the mutation that make them resistant to treatment have also picked up the chromosomal deletions that make them invisible to the diagnostic tests. This means that it will be harder to detect people who are infected, and then when infected people are treated with antimalarial drugs, that may not work to stop them from spreading the disease.”

Jeffrey Bailey, Study Author and Associate Professor, Translational Research and Pathology and Laboratory Medicine, Brown Univesity

Rapid diagnostic tests that identify highly expressed particular parasite proteins in the blood are the typical way to diagnose malaria in Africa. Even if the patient is asymptomatic, the tests can still detect malaria. Since they lack the genes for these proteins, the parasites have evolved to be undetectable by the tests.

The World Health Organization recommends a combination therapy comprising artemisinin-based drug compounds as the first-line malaria treatment, which is particularly successful in avoiding mortality and minimizing transmission. The mutations discovered in Africa currently confer resistance to artemisinin.

Bailey’s Brown University research team worked closely with researchers from the Ethiopian Public Health Institute and the University of North Carolina at Chapel Hill to perform a comparative genomic analysis of malaria parasite samples with deleted protein-expressing genes collected across three regions of Ethiopia.

The scientists, led by Bailey, co-director of the PhD program at Brown’s Center for Computational Molecular Biology, employed molecular sequencing to analyze the incidence of mutations that confer artemisinin resistance. Abebe Fola, a postdoctoral researcher in Bailey’s group, was a key contributor to this study and is the study’s first author.

They discovered that 8.2% of drug-resistant parasites also had deletions in the protein-expressing gene, making them identifiable by diagnostic testing.

Although the general incidence of malaria in Ethiopia is low, the disease is nevertheless prevalent across 75% of the country, with 65% of the people at risk. Every year, more than 5 million cases of malaria are reported.

The Ethiopian government has set a goal of eliminating malaria by 2030, and timely diagnosis and treatment with appropriate drugs is a key component of the malaria eradication campaign.

Bailey added, “The spread of these parasites will certainly make eliminating malaria in Ethiopia and elsewhere in Africa more difficult and will likely lead to increased cases and deaths.”

The researchers came to the conclusion that close monitoring of the spread of combined drug- and diagnostic-resistant parasites is required, noting that a better understanding of how these mutations emerge, interact, and spread is vital for ensuring the efficacy of future malaria control and elimination efforts across Africa.

Furthermore, Bailey stated that there is an urgent need to find new malaria treatments, in addition to artemisinin, as well as vaccinations to prevent and reduce the spread of the disease.

According to Bailey, the development and refining of next-generation sequencing has substantially improved the capacity to undertake genomic surveillance to track mutations while searching for new ones.

His lab at Brown University invented high-throughput methods to sequence a large number of genes simultaneously, and it has been working with research groups from other institutions as well as health organizations in nations like Uganda on initiatives like the current study.

While the analysis for this study was carried out at Brown University, Bailey and the other members of the research team are trying to improve Ethiopia and other African countries’ ability to undertake genomic surveillance.