KATHMANDU, Aug 25: Scientists have identified new genetic mutations in malaria parasites that may be making commonly used malaria drugs less effective, raising concerns over the growing threat of drug-resistant malaria.
A study led by scientists at Brown University examined the entire genetic makeup of malaria-causing parasites collected from the blood of hundreds of malaria patients in Uganda. The researchers found that genetic changes in some parasites were associated with reduced sensitivity to drugs widely used to treat malaria in Africa and the United States.
The findings were recently published in the journal Nature Medicine.
“It is concerning to see these new genetic changes spreading so rapidly. This suggests that these changes may be important for the parasites’ survival,” said Jeffrey Bailey, associate professor at Brown University and one of the study’s authors, in a statement released by the university.
Bailey noted that malaria continues to cause a large number of deaths, particularly in sub-Saharan Africa. As drug resistance increases, malaria-control programs could become less effective, putting more lives at risk.
Why are malaria drugs losing their effectiveness?
Drug resistance typically develops when medicines are widely used to treat diseases caused by bacteria, viruses or parasites. Because malaria drugs are extensively used across Africa, some parasites have developed genetic changes that help them survive exposure to the medicines.
Malaria-free Asia Pacific is within our Reach
According to Bailey, scientists are therefore working to develop systems to monitor genetic changes in disease-causing organisms and track how those changes affect drug effectiveness over time.
The Brown University research team has played an important role in developing a genomic surveillance system that can identify genetic changes in malaria parasites by analyzing their DNA. Genomic surveillance involves regularly tracking genetic changes in disease-causing organisms to detect emerging risks.
Study uncovers new clues
Until now, scientists monitoring malaria drug resistance have generally focused on a limited number of known biological markers. Brown University researcher Karamoko Niaré, however, decided to examine the parasite’s entire genome.
“We knew that the parasite was changing over time and that malaria drugs were becoming less effective, but we wanted to understand the exact genetic reasons behind this,” Niaré said.
Studying the entire genome provided a clearer picture of the changes occurring within the parasite, he said.
New genetic markers identified
Artemether-lumefantrine has been the main treatment for uncomplicated malaria in Uganda for the past two decades. It is an artemisinin-based combination therapy (ACT), in which two or more drugs are used together to kill malaria parasites.
By 2026, the US Centers for Disease Control and Prevention (CDC) had recommended extending the treatment period for some people returning from travel to Africa after standard treatment was found to be insufficient in fully clearing the infection. The development has raised concerns that malaria parasites are becoming less sensitive to the drugs.
The researchers identified a specific region of the malaria parasite’s genome containing 69 genes. Further genetic analysis showed that a combination of three specific mutations and two gene deletions was associated with reduced drug effectiveness.
These genetic changes were found to reduce the parasite’s sensitivity to artemisinin, lumefantrine and another antimalarial drug, mefloquine. The researchers found that the changes were primarily located in a gene known as PX1.
The study is the first to establish a link between reduced sensitivity to drugs used in malaria combination therapies and specific genetic changes in the parasite.
“We did not have a validated genetic marker associated with lumefantrine resistance. Our study has identified an important marker that can be used to monitor the spread of reduced sensitivity to the major malaria treatment drugs across Africa,” Niaré said.
More research needed
The scientists have called for the newly identified mutations to be incorporated into drug-resistance surveillance systems and for further research into their implications.
As the study was conducted in laboratory conditions using parasites collected from patients, further research is needed to determine how parasites carrying these genetic changes affect treatment outcomes in actual patients, Bailey said.
According to Bailey, the genetic changes appear to be spreading rapidly in Uganda. However, it remains unclear how widely they have spread to other countries beyond Uganda.
“This highlights the need to develop models to predict when these drugs could become completely ineffective,” Bailey said, adding that there is also an urgent need to develop new medicines for treating malaria.
Scientists from Johns Hopkins University, Uganda’s Infectious Diseases Research Collaboration, the University of California, San Francisco, the University of North Carolina and the University of Notre Dame also contributed to the study.
