A Brown-led team of scientists has discovered changes in malaria-causing parasites, complicating efforts to eradicate the illness in Africa.
Malaria is a potentially fatal illness conveyed to people by certain species of mosquitos.
Brown University, PROVIDENCE, R.I.
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 monitoring research. Scientists had already discovered strains of the parasite that causes 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 spread independently, but the new study is the first published report to confirm the prevalence of this type of double-resistant malaria strain, according to study author Jeffrey Bailey, an associate professor of translational research and pathology and laboratory medicine at Brown University.
“Now we’re essentially seeing the worst-case scenario: parasites with the mutation that makes them resistant to treatment have also picked up the chromosomal deletions that make them invisible to diagnostic tests,” Bailey explained. “This means that it will be more difficult to detect infected people, and that when infected people are treated with antimalarial drugs, they may not work to prevent the disease from spreading.”
In Africa, fast diagnostic tests that identify certain parasite proteins in the blood that are highly expressed are used to diagnose malaria. Even if the patient is asymptomatic, the tests can prove malaria. The parasites that lack these genes have evolved to be invisible to the tests.
The World Health Organization recommends a combination therapy comprising artemisinin-based pharmacological 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 conduct 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 Ph.D. 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 paper’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 illness is nevertheless prevalent across 75% of the nation, 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 medications is a key component of the malaria eradication campaign.
“The spread of these parasites will undoubtedly make malaria elimination in Ethiopia and elsewhere in Africa more difficult, and will almost certainly lead to an increase in cases and deaths,” Bailey said.
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 critical to the success 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 illness.
With the development and refining of next-generation sequencing, the capacity to undertake genomic surveillance to monitor mutations while hunting for new ones has considerably progressed over the previous decade, according to Bailey. His Brown group pioneered high-throughput techniques for sequencing multiple genes at once, and he has collaborated on studies like this one with teams from other institutions as well as health organizations in countries like Uganda. While this study’s analysis was carried out at Brown, Bailey and other members of the research team are striving to strengthen genomic monitoring capabilities in Ethiopia and other regions of Africa.