Genomic surveillance has uncovered mutations in malaria-causing parasites in Ethiopia that pose challenges to eradicating the disease in Africa.

Researchers said they had identified new strains of parasites that are resistant to current treatments and can evade locally available diagnostic tests — a development that could lead to an increase in malaria cases and deaths, and make the elimination of the disease even more difficult.

Scientists from Ethiopia and Brown University who conducted a genomic surveillance study, published their findings in Nature Microbiology on Monday.

Prior to this study, resistant strains of the malaria parasite had been found in Uganda, Tanzania, and Rwanda, as well as diagnostic test-resistant parasites in the Horn of Africa. However, this is the first report confirming the prevalence of double-resistant malaria strains.

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The undetectability

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

The parasites’ resistance to treatment and invisibility to diagnostic tests pose a predicament for the region which is already one of the worst affected by the disease. According to the scientists, detection of infected individuals becomes harder, and the effectiveness of antimalarial drugs in stopping the spread of the disease is compromised.

“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,” Bailey said. “This means it will be harder to detect infected people, and then when infected people are treated with antimalarial drugs, that may not work to stop them from spreading the disease.”

The standard method for diagnosing malaria involves rapid diagnostic tests that detect specific parasite proteins in the blood. These tests can identify malaria. However, the parasites lacking the genes for these proteins have evolved to be undetectable by these tests.

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First-line treatment recommended by the WHO involves artemisinin-based drug compounds. These drugs are effective in preventing death and reducing transmission. However, the mutations observed in the region confer resistance to artemisinin.

The research team discovered that 8.2 percent of drug-resistant parasites also carried deletions of the protein-expressing gene that made them detectable by the diagnostic tests.

Although malaria incidence in Ethiopia is low overall, the disease remains endemic in 75 percent of the country, putting 65 percent of the population at risk.

With over 5 million malaria episodes occurring annually, the Ethiopian government aims to eliminate malaria by 2030. Prompt diagnosis and treatment with effective drugs are crucial components of the elimination programme.

The team led by Bailey, co-director of the PhD. program at Brown’s Center for Computational Molecular Biology, and Abebe Fola, a postdoctoral researcher in Bailey’s lab, the scientists used molecular sequencing to assess the prevalence of mutations that confer resistance to Artemisinin.

According to the latest World Health Organization (WHO) Malaria Report, there were 247 million cases of malaria in 2021 compared with 245 million cases in 2020. The estimated number of malaria deaths stood at 619 000 in 2021 versus 625 000 in 2020.

The WHO African Region carries a disproportionately high share of the global malaria burden. In 2021, the region was home to 95 percent of malaria cases and 96 percent of malaria deaths. Children under five are the worst affected, accounting for about 80 percent of all malaria deaths in the region.

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Four African countries accounted for just over half of all malaria deaths worldwide: Nigeria (31.3 percent), the Democratic Republic of the Congo (12.6 percent), United Republic of Tanzania (4.1 percent) and Niger (3.9 percent).

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

The scientists concluded that close monitoring of the spread of combined drug- and diagnostic-resistant parasites is needed, noting that improved understanding of how these mutations emerge, interact and spread is critical to the success of future malaria control and elimination efforts across the continent.

In addition to monitoring, Bailey said, there is an urgent need to develop new therapies and vaccines to combat malaria, stressing the importance of genomic surveillance in tracking mutations and identifying new ones.

Next-generation sequencing has significantly advanced the ability to conduct such surveillance. The team at Brown University has pioneered high-throughput techniques for sequencing multiple genes simultaneously and is collaborating with other universities and health agencies in countries like Uganda. While the analysis for this study was conducted at Brown, efforts are underway to build the capacity for genomic surveillance in Ethiopia and other parts of Africa.