Treatment Resistant Malaria Parasites Found in Ethiopia

New strains of malaria-causing parasites that are resistant to current treatments and undetectable by standard diagnostic tests have been found by scientists in Ethiopia. This development could lead to an increase in cases and deaths from malaria and make the persistent disease’s eradication even more difficult.

In Nature Microbiology, the scientists described the results of a genomic monitoring investigation. Scientists had already discovered strains of the parasite that causes malaria in Uganda, Tanzania, and Rwanda that were resistant to the majority of antimalarial medications on the market. Separately, malaria parasites resistant to diagnostic testing had arisen in the Horn of Africa.

According to study author Jeffrey Bailey, an associate professor of translational research, pathology, and laboratory medicine at Brown University, although those parasites have been spreading independently of one another, the new study is the first published report to confirm the prevalence of this type of double-resistant malaria strain.

“Now we’re 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,” Bailey said. “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.”

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.

A combination therapy with artemisinin-based pharmacological compounds is the first-line malaria treatment advised by the World Health Organization and is frequently extremely effective in preventing death and minimizing transmission. Artemisinin resistance has recently been discovered in Africa due to mutations.

In close collaboration with scientists from the Ethiopian Public Health Institute and the University of North Carolina at Chapel Hill, Bailey’s research team at Brown carried out a comparative genomic analysis of malaria parasite samples that had been collected from three different regions of Ethiopia and contained the deleted protein-expressing genes. The researchers employed molecular sequencing to determine the prevalence of mutations that give resistance to artemisinin under the direction of Bailey, co-director of the Ph.D. program at Brown’s Center for Computational Molecular Biology. This work was greatly assisted by Abebe Fola, a postdoctoral researcher in Bailey’s group, who is also the paper’s first author.

They discovered that 8.2% of drug-resistant parasites also had the gene deletions that allowed the diagnostic tests to identify them as being protein-expressing parasites.

Although there is a low overall incidence of malaria in Ethiopia, it is nevertheless prevalent across 75% of the nation, putting 65% of the population at risk. Each year, there are more than 5 million cases of malaria. The Ethiopian government established a target for the eradication of malaria by 2030, and a key component of the campaign to do so is timely identification and treatment with potent medications.

“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,” Bailey said.

The researchers came to the conclusion that close monitoring of the spread of parasites that are both drug- and diagnostic-resistant is required. They also noted that the success of future malaria control and elimination initiatives in Africa depends on having a better understanding of how these mutations emerge, interact, and spread.

In addition, Bailey added, there is a pressing need to create new treatments for malaria in addition to artemisinin as well as vaccinations to stop and reduce the disease’s spread.

According to Bailey, the development and refinement of next-generation sequencing has substantially improved the ability 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 universities 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 genetic monitoring.

The Ministry of Health of Ethiopia (EPHI5405), the Bill and Melinda Gates Foundation through the World Health Organization (OPP1209843), and the U.S. National Institutes of Health (R01AI132547, K24AI134990, R01AI1777791) all contributed funding to the project.

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