Resistant malaria parasites become increasingly prevalent across Ethiopia

Researchers from the University of North Carolina at Chapel Hill's Institute for Global Health and Infectious Diseases, the Ethiopian Public Health Institute (EPHI), Brown University, the University of Notre Dame, and Ethiopia's Ministry of Health have found that malaria parasites carrying genetic markers associated with resistance to frontline antimalarial medicines and commonly used diagnostic tests are becoming increasingly prevalent across Ethiopia. Led by Ashenafi Assefa, PhD, and Jonathan B. Parr, MD, MPH, the findings published in the Journal of the American Medical Association come amid a dramatic resurgence of malaria in the country, which reported more than 10 million malaria cases in 2024 compared with fewer than 1 million in 2019.  

The study 

To investigate factors contributing to the resurgence, researchers conducted a nationwide survey at 20 sentinel sites across 11 Ethiopian regions during July and August 2024. More than 2,200 patients with symptomatic malaria were enrolled, and parasite samples were analyzed for genetic markers associated with resistance to antimalarial drugs and detection by malaria diagnostic tests.  

The study focused on mutations in Plasmodium falciparum, the deadliest malaria parasite species, including markers linked to partial resistance to first-line artemisinin-based therapies and genetic deletions that allow parasites to evade detection by widely used HRP2-based rapid diagnostic tests.  

The findings

Researchers found that the prevalence of the most common artemisinin-resistance mutation in Ethiopia, known as pfk13, R622I, has increased substantially compared with previous years. They also identified a growing prevalence of parasites carrying deletions of the pfhrp2 and pfhrp3 genes, which can cause false-negative results on HRP2-based rapid diagnostic tests.  

Genetic analyses revealed that multiple resistant parasite lineages are circulating and expanding across the country. However, the findings suggest that resistance alone is unlikely to explain Ethiopia's recent malaria resurgence. Instead, the results point to a combination of factors, including disruptions to malaria control programs and climatic changes, contributing to increased transmission.  

Our findings show that malaria parasites carrying drug- and diagnostic-resistance mutations are becoming increasingly common in Ethiopia, raising important concerns for the future of malaria control in the region. At the same time, the data suggest these mutations were not the primary cause of the recent resurgence in malaria cases. Continued investment in prevention, diagnosis and new treatment regimens are essential to protect recent gains and stay ahead of emerging resistance."  

Jonathan B. Parr, MD, MPH, co-senior author of the study and associate professor of medicine

Among participants with confirmed malaria infections, nearly two-thirds were infected with P. falciparum. Approximately one-quarter of successfully genotyped parasites carried deletions that enable them to escape detection by HRP2-based rapid tests, while resistance-associated mutations were observed across multiple regions of the country. The findings support Ethiopia's recent decision to adopt alternative malaria rapid diagnostic tests that do not rely solely on HRP2 detection. The researchers note that ongoing monitoring of resistance markers will be critical to malaria treatment and control strategies.  

"Efforts to address the rise in malaria cases in Ethiopia are already showing encouraging results," Assefa said. "But the increasing prevalence of resistance-associated mutations underscores the importance of strengthening surveillance systems and evaluating new treatment approaches before resistance becomes a larger threat." 

The study was supported by the World Bank's Africa CDC Regional Investment Financing Project and the U.S. National Institutes of Health. Preliminary findings have already provided critical input for frontline workers and federal program managers.