A Case Definition for Post-Artemisinin Delayed Hemolysis: Information for Healthcare Professionals

New research by Jauréguiberry et al. supports the clinical experience on the overall safety of artesunate for treatment of severe malaria.

Artesunate is a highly effective intravenous medicine from the artemisinin class of anti-malarials. Oral artemisinin compounds in combination therapy and the parenteral counterparts, artesunate and artemether, have become essential tools in the treatment and control of malaria worldwide.

Unexpected brief episodes of hemolytic anemia occurring weeks after treatment of severe malaria with artesunate have been reported in some patients, but it has been challenging to determine why this might be occurring. These hemolytic episodes were usually at least a week after the symptoms of malaria and parasitemia had resolved, so it did not seem to be a direct effect of the malaria treatment. The syndrome has been termed post-artesunate delayed hemolysis (PADH), and is characterized by >10% decline in hemoglobin levels occuring more than 1 week after treatment initiation.

Research by Jauréguiberry et al. provides evidence that PADH is the result of the normal removal from the blood stream of once-infected erythrocytes (o-IEs) whose parasites have been killed by artesunate and removed by the spleen. The greatly shortened lifespan of the o-IEs results in a brief drop in hemoglobin as the damaged cells are removed. Although tests for o-IEs are not available to clinicians at this point, it is possible that testing for o-IEs could identify at-risk patients immediately after initial treatment to identify impending instances of hemolytic anemia and target those patients for appropriate follow up.

Dr. Paul Arguin of CDC, in an accompanying editorial, notes, “PADH does not seem to be a direct effect of artemisinin derivative drugs.  These erythrocytes were already sentenced to death when they were infected by malaria parasites and artesunate allowed these infected erythrocytes a temporary stay of execution.” Artesunate remains among the most effective treatment options for severe malaria in countries where it is licensed for use. However, clinicians should be aware of PADH and consider PADH in patients with hemolysis in the weeks after artesunate treatment.

To view the CDC editorial on post-artemisin delayed hemolysis, see Case definition: postartemisinin delayed hemolysis

To view the study by Jauréguiberry, et al., see Post-artesunate delayed hemolysis is a predictable event related to the live-saving effect of artemisinins