Volume 96, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Recently, 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.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. World Health Organization, 2009. World Malaria Report. Available at: http://apps.who.int/iris/bitstream/10665/44234/1/9789241563901_eng.pdf. Accessed June 9, 2016. [Google Scholar]
  2. Sylla K, Abiola A, Tine RC, Faye B, Sow D, Ndiaye JL, Ndiaye M, Lo AC, Folly K, Ndiaye LA, Gaye O, , 2013. Monitoring the efficacy and safety of three artemisinin based-combinations therapies in Senegal: results from two years surveillance. BMC Infect Dis 13: 598607.[Crossref] [Google Scholar]
  3. Briggs M, Arguin PM, , 2013. Published reports of delayed hemolytic anemia after treatment with artesunate for severe malaria–worldwide, 2010–2012. MMWR Morb Mortal Wkly Rep 62: 58. [Google Scholar]
  4. Paczkowski MM, Landman KL, Arguin PM, , 2014. Update on cases of delayed hemolysis after parenteral artesunate therapy for malaria, United States, 2008 and 2013. MMWR Morb Mortal Wkly Rep 63: 753755. [Google Scholar]
  5. Burri C, Ferrari G, Ntuku HM, Kitoto AT, Duparc S, Hugo P, Mitembo DK, Lengeler C, , 2014. Delayed anemia after treatment with injectable artesunate in the Democratic Republic of the Congo: a manageable issue. Am J Trop Med Hyg 91: 821823.[Crossref] [Google Scholar]
  6. Jarvis JN, Coltart CE, Pule M, Chiodini PL, Doherty T, , 2013. Artemisinin therapy and severe delayed haemolysis. Lancet 382: 180.[Crossref] [Google Scholar]
  7. De Nardo P, Oliva A, Giancola ML, Ghirga P, Mencarini P, Bibas M, Nicastri E, Antinori A, Corpolongo A, , 2013. Haemolytic anemia after oral artemether-lumefantrine treatment in a patient affected by severe imported falciparum malaria. Infection 41: 863865.[Crossref] [Google Scholar]
  8. Corpolongo A, De Nardo P, Ghirga P, Gentilotti E, Bellagamba R, Tommasi C, Paglia MG, Nicastri E, Narciso P, , 2012. Haemolytic anemia in an HIV-infected patient with severe falciparum malaria after treatment with oral artemether-lumefantrine. Malar J 11: 9194.[Crossref] [Google Scholar]
  9. Jauréguiberry S, Ndour PA, Roussel C, Ader F, Safeukui I, Nguyen M, Biligui S, Ciceron L, Mouri O, Kendjo E, Bricaire F, Vray M, Angoulvant A, Mayaux J, Haldar K, Mazier D, Danis M, Caumes E, Thellier M, Buffet P, French Artesunate Working Group; , 2014. Postartesunate delayed hemolysis is a predictable event related to the lifesaving effect of artemisinins. Blood 124: 167175.[Crossref] [Google Scholar]
  10. Arguin PM, , 2014. Case definition: postartemisinin delayed hemolysis. Blood 124: 157158.[Crossref] [Google Scholar]
  11. Rehman K, Lötsch F, Kremsner PG, Ramharter M, , 2014. Haemolysis associated with the treatment of malaria with artemisinin derivatives: a systematic review of current evidence. Int J Infect Dis 29: 268273.[Crossref] [Google Scholar]
  12. Laura R, Phillipe L, Marie-Pierre H, Scientific Study Group for Travel Medicine; , 2013. A Case of Hemolytic Anemia after Severe Malaria Successfully Treated with Artesunate. Joint Symposium belgische vereniging voor infectiologie en klinische microbiologie. Available at: http://www.sbimc.org/posters%202013/Abstract5.pdf. Accessed June 9, 2016. [Google Scholar]
  13. Raffray L, Receveur MC, Beguet M, Lauroua P, Pistone T, Malvy D, , 2014. Severe delayed autoimmune haemolytic anaemia following artesunate administration in severe malaria: a case report. Malar J 13: 398403.[Crossref] [Google Scholar]
  14. Rolling T, Agbenyega T, Issifou S, Adegnika AA, Sylverken J, Spahlinger D, Ansong D, Löhr SJ, Burchard GD, May J, Mordmüller B, Krishna S, Kremsner PG, Cramer JP, , 2014. Delayed hemolysis after treatment with parenteral artesunate in African children with severe malaria–a double-center prospective study. J Infect Dis 209: 19211928.[Crossref] [Google Scholar]
  15. Neuman G, Boodhan S, Wurman I, Koren G, Bitnun A, Kirby-Allen M, Ito S, , 2014. Ceftriaxone-induced immune hemolytic anemia. Ann Pharmacother 48: 15941604.[Crossref] [Google Scholar]
  16. Garratty G, , 2010. Immune hemolytic anemia associated with drug therapy. Blood Rev 24: 143150.[Crossref] [Google Scholar]
  17. Imam SN, Wright K, Bhoopalam N, Choudhury A, , 2008. Hemolytic anemia from ceftriaxone in an elderly patient: a case report. J Am Med Dir Assoc 9: 610611.[Crossref] [Google Scholar]
  18. Kudoh T, Nagata N, Suzuki N, Nakata S, Chiba S, Takahashi T, , 1994. Minocycline-induced hemolytic anemia. Acta Paediatr Jpn 36: 701704.[Crossref] [Google Scholar]
  19. Tran TH, Day NP, Ly VC, Nguyen TH, Pham PL, Nguyen HP, Bethell DB, Dihn XS, Tran TH, White NJ, , 1996. Blackwater fever in southern Vietnam: a prospective descriptive study of 50 cases. Clin Infect Dis 23: 12741281.[Crossref] [Google Scholar]
  20. Van den Ende J, Coppens G, Verstraeten T, Van Haegenborgh T, Depraetere K, Van Gompel A, Van den Enden E, Clerinx J, Colebunders R, Peetermans WE, Schroyens W, , 1998. Recurrence of blackwater fever: triggering of relapses by different antimalarials. Trop Med Int Health 3: 632639.[Crossref] [Google Scholar]
  21. Zoller T, Junghanss T, Kapaun A, Gjorup I, Richter J, Hugo-Persson M, Mørch K, Foroutan B, Suttorp N, Yürek S, Flick H, , 2011. Intravenous artesunate for severe malaria in travelers, Europe. Emerg Infect Dis 17: 771777.[Crossref] [Google Scholar]
  22. Yansouni CP, Libman MD, , 2015. Does post-artesunate delayed haemolysis change practice? Travel Med Infect Dis 13: 122123.[Crossref] [Google Scholar]
  23. Rolling T, Agbenyega T, Krishna S, Kremsner PG, Cramer JP, , 2015. Delayed haemolysis after artesunate treatment of severe malaria: review of the literature and perspective. Travel Med Infect Dis 13: 143149.[Crossref] [Google Scholar]
  24. Kreeftmeijer-Vegter AR, van Genderen PJ, Visser LG, Bierman WF, Clerinx J, van Veldhuizen CK, de Vries PJ, , 2012. Treatment outcome of intravenous artesunate in patients with severe malaria in The Netherlands and Belgium. Malar J 11: 102112.[Crossref] [Google Scholar]
  25. Eder M, Farne H, Cargill T, Abbara A, Davidson RN, , 2012. Intravenous artesunate versus intravenous quinine in the treatment of severe falciparum malaria: a retrospective evaluation from a UK centre. Pathog Glob Health 106: 181187.[Crossref] [Google Scholar]
  26. Caramello P, Balbiano R, De Blasi T, Chiriotto M, Deagostini M, Calleri G, , 2012. Severe malaria, artesunate and haemolysis. J Antimicrob Chemother 67: 20532054.[Crossref] [Google Scholar]

Data & Media loading...

  • Received : 09 Jun 2016
  • Accepted : 22 Dec 2016
  • Published online : 13 Feb 2017

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error