Malaria treatment failures linked to host red blood cells: RGCB study
For decades, artemisinin-based combination therapies have been the standard treatment for malaria worldwide. However, scientists have observed that some patients fail to clear the malaria parasite (Plasmodium falciparum) and experience relapse even after receiving the correct treatment, despite no detectable genetic mutations in the parasite that would indicate drug resistance.
Researchers at the Rajiv Gandhi Centre for Biotechnology (RGCB) in Thiruvananthapuram may have found an explanation. Their study, published in the Journal of Infectious Diseases on June 16 as an Editor's Choice article, suggests that host factors—specifically the type of red blood cells present in the patient—can enable the parasite to survive artemisinin treatment.
The research team, led by Christeen Davis and senior author Rajesh Chandramohanadas, demonstrated that the malaria parasite prefers to invade young red blood cells known as reticulocytes. These cells are rich in antioxidants, nutrients, and protective enzymes that can neutralise oxidative stress. Artemisinin kills the parasite by generating a flood of free radicals that cause oxidative damage. However, in the antioxidant-rich environment of reticulocytes, the parasites multiply faster and are able to withstand and recover from artemisinin-induced damage far more effectively than in mature red blood cells.
Critically, when the researchers transferred the parasites from reticulocytes into mature red blood cells, the protective effect disappeared, confirming that the resistance was driven by the host cell environment rather than permanent genetic changes in the parasite.
“Our findings demonstrate that the biology of the host cell can significantly influence how malaria parasites respond to treatment. The parasite is not acting alone. It exploits the natural antioxidant defences present in young blood cells to protect itself from drug-induced stress,” said Dr. Chandramohanadas.
The study has particular clinical relevance for children, anaemic patients, and individuals recovering from blood loss or infection, who often have elevated levels of reticulocytes in circulation. These are the patients in whom the malaria parasite may persist despite treatment.
Researchers believe that future malaria therapies may benefit from targeting host-parasite interactions in addition to the parasite itself. Understanding how parasites exploit antioxidant pathways within reticulocytes could open new avenues for improving the effectiveness of existing antimalarial drugs and reducing treatment failures.
