A team of scientists led by Brown University conducted genomic surveillance and discovered mutations in the parasite that causes malaria that are likely to challenge efforts to eradicate malaria in Africa. Scientists have discovered new variants of the malaria parasite in Ethiopia that are resistant to existing treatments and undetectable by standard diagnostic tests. The situation could lead to an increase in malaria cases and deaths, complicating efforts to eradicate the disease.

The authors detailed the results of their genome surveillance study in the journal Nature Microbiology. Scientists have discovered strains of the malaria parasite that are resistant to most existing antimalarial drugs in Uganda, Tanzania and Rwanda; malaria parasites that are resistant to diagnostic tests have also emerged in the Horn of Africa.

The parasites have been circulating independently of each other, but the new study is the first published report confirming the prevalence of this dual-resistant strain of malaria, said study author Jeffrey Bailey, associate professor of translational research and pathology and laboratory medicine at Brown.

"Right now, we're basically seeing a worst-case scenario: Parasites have mutations that make them resistant to treatments, as well as chromosomal deletions that make them undetectable by diagnostics," Bailey said. "That means it will be harder to detect infected people, and then when infected people are treated with antimalarial drugs, it may not be possible to stop them from spreading the disease."

Diagnostic Difficulties and Treatment Resistance

In Africa, the standard way to diagnose malaria is through rapid diagnostic tests that detect specific parasite proteins that are highly expressed in the blood. The test can confirm malaria even if the patient has no symptoms. Parasites lacking genes for these proteins have evolved to undetectable levels.

The first-line treatment for malaria recommended by the World Health Organization is artemisinin-based combination therapy, which is highly effective in preventing death and reducing transmission. The variant currently found in Africa confer resistance to artemisinin.

Bailey's research group at Brown University, working closely with researchers at the Ethiopian Public Health Institute and the University of North Carolina at Chapel Hill, conducted a comparative genome analysis of samples of malaria parasites with deleted protein expression genes collected from three regions in Ethiopia. Led by Bailey, co-director of the doctoral program at Brown's Center for Computational Molecular Biology, the scientists used molecular sequencing technology to assess the prevalence of artemisinin-resistant mutations. Abebe Fola, a postdoctoral researcher in Bailey's lab who played an important role in this work and is the paper's first author.

Study results and malaria prevalence in Ethiopia

They found that 8.2% of the resistant parasites also carried deletions in protein-expressing genes that allowed them to be detected by diagnostic tests.

In Ethiopia, the overall incidence of malaria is low, but it is still endemic in 75% of the country and 65% of the population is at risk. There are more than 5 million malaria attacks each year. The Ethiopian government has set a goal of eliminating malaria by 2030, and timely diagnosis and use of effective drug treatment are the cornerstones of the malaria elimination plan.

"The spread of these parasites will certainly make it more difficult to eliminate malaria in Ethiopia and other parts of Africa and could lead to an increase in cases and deaths," Bailey said.

The spread of drug-resistant and diagnostic-resistant combination parasites needs to be closely monitored, the scientists concluded, noting that a better understanding of how these variants emerge, interact and spread will be critical for future efforts to successfully control and eliminate malaria in Africa.

In addition, Bailey said there is an urgent need to develop new treatments for malaria in addition to artemisinin, as well as vaccines to prevent and slow the spread of the disease. Over the past decade, with the advent and refinement of next-generation sequencing technologies, the ability to perform genomic surveillance to monitor mutations while looking for new mutations has greatly improved. His lab at Brown University has pioneered the use of high-throughput techniques to sequence many genes simultaneously, and has collaborated with research teams at other universities and health agencies in countries such as Uganda on projects like this study. While the analysis for this study was conducted at Brown University, Bailey and other members of the research team are working to build genomic surveillance capabilities in Ethiopia and other parts of Africa.

Compiled source: ScitechDaily