Published reports of delayed hemolytic anemia after treatment with artesunate for severe malaria--worldwide, 2010-2012.

Artesunate has been recommended by the World Health Organization (WHO) as the first-line treatment for severe malaria since 2010. It is not licensed in the United States but is available from CDC under an investigational new drug (IND) protocol. During 2010-2012, a total of 19 cases of delayed hemolytic anemia after treatment of severe malaria with artesunate were published in the peer-reviewed medical literature, but no such cases have been reported in the United States. CDC Malaria Branch staff reviewed each published report of delayed hemolysis after artesunate use. Based on the pathogenesis of malaria, the hemolysis likely is a result of severe malaria and not the treatment itself. However, artesunate used in the United States is produced by the U.S. Army Medical Materiel Development Activity, and artesunate used outside of the United States is not. An unrecognized difference might exist between the U.S. artesunate and the artesunate used elsewhere. Alternatively, cases of artesunate-associated hemolysis might have occurred in the United States but were not reported. To better assess these possibilities, CDC has amended the artesunate IND protocol and now recommends that persons treated for severe malaria with artesunate be followed for 4 weeks after treatment and evaluated for hemolytic anemia.