title: Development of Delayed Hemolytic Anemia After Treatment with Oral Artemether-Lumefantrine in Two Patients with Severe Falciparum Malaria.
abstract: AbstractRecently, reports of delayed hemolytic anemia after treatment with artemisinin and its derivatives have emerged. Here we report two cases of delayed hemolytic anemia in a patient with severe falciparum malaria after treatment with oral artemether-lumefantrine (AL). The first patient, a 20-year-old Japanese male student, was diagnosed with falciparum malaria and was administered AL. As having a high parasitemia rate (20.6%) was the only severe malaria criterion met in this case and his general condition was stable, we continued with AL treatment. Despite disappearance of malarial parasites after 4 days of AL administration, a persistent fever remained. On days 13 and 16, a diagnosis of hemolytic anemia was made (lactate dehydrogenase [LDH]: 1,466 U/L, hemoglobin [Hb]: 7.2 g/dL). A blood smear at that time revealed no parasites. He recovered naturally from delayed hemolysis. The second patient, a 27-year-old Japanese female student, was diagnosed with falciparum malaria (parasitemia: 4.5%) and treated initially with oral quinine hydrochloride and doxycycline. The following day, parasitemia increased to 7.9% and oral AL was initiated. She was discharged on day 4 after achieving parasite clearance and afebrility. However, on day 5, fever (body temperature > 38°C) recurred, and on day 11, a diagnosis of hemolytic anemia was made (LDH: 712 U/L, Hb: 8.8 g/dL). A follow-up confirmed that her condition improved gradually. AL treatment of severe malaria can cause delayed hemolytic anemia. Patients should be followed up for up to 4 weeks to detect signs of hemolysis and provide appropriate symptomatic treatment.
authors.affiliation: Department of Infectious Diseases, Kyoto City Hospital, Kyoto, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsuchido
authors.affiliation: Center for Infectious Diseases, Nara Medical University, Nara, Japan.|Department of Pathogen, Infection and Immunity, Nara Medical University, Nara, Japan.
authors.forename: Fukumi
authors.initials: F
authors.lastname: Nakamura-Uchiyama
authors.affiliation: Center for Infectious Diseases, Nara Medical University, Nara, Japan.
authors.forename: Kasumi
authors.initials: K
authors.lastname: Toyoda
authors.affiliation: Department of Tropical Medicine and Malaria, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Moritoshi
authors.initials: M
authors.lastname: Iwagami
authors.affiliation: Department of Infectious Diseases, Kyoto City Hospital, Kyoto, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tochitani
authors.affiliation: Department of Infectious Diseases, Kyoto City Hospital, Kyoto, Japan.
authors.forename: Koh
authors.initials: K
authors.lastname: Shinohara
authors.affiliation: Center for Infectious Diseases, Nara Medical University, Nara, Japan.
authors.forename: Naokuni
authors.initials: N
authors.lastname: Hishiya
authors.affiliation: Center for Infectious Diseases, Nara Medical University, Nara, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Ogawa
authors.affiliation: Center for Infectious Diseases, Nara Medical University, Nara, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Uno
authors.affiliation: Center for Infectious Diseases, Nara Medical University, Nara, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Kasahara
authors.affiliation: Department of Pathogen, Infection and Immunity, Nara Medical University, Nara, Japan.
authors.forename: Yukiteru
authors.initials: Y
authors.lastname: Ouji
authors.affiliation: Department of Tropical Medicine and Malaria, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kano
authors.affiliation: Center for Infectious Diseases, Nara Medical University, Nara, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Mikasa
authors.affiliation: Department of Infectious Diseases, Kyoto City Hospital, Kyoto, Japan.
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Pathogen, Infection and Immunity, Nara Medical University, Nara, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Yoshikawa
authors.affiliation: Department of Infectious Diseases, Division of Parasitology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Maruyama
mesh_terms: D000328:Adult; D000743:Anemia, Hemolytic / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage / Q000009:adverse effects*; D001772:Blood Cell Count; D003289:Convalescence; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000009:adverse effects*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D008297:Male; D018512:Parasitemia / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D013997:Time Factors
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D006454:Hemoglobins; D007770:L-Lactate Dehydrogenase