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Delayed-Onset Hemolytic Anemia in Patients with Travel-Associated Severe Malaria Treated with Artesunate, France, 2011–2013 - Volume 21, Number 5—May 2015 - Emerging Infectious Disease journal - CDC

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Delayed-Onset Hemolytic Anemia in Patients with Travel-Associated Severe Malaria Treated with Artesunate, France, 2011–2013 - Volume 21, Number 5—May 2015 - Emerging Infectious Disease journal - CDC





Volume 21, Number 5—May 2015

Research

Delayed-Onset Hemolytic Anemia in Patients with Travel-Associated Severe Malaria Treated with Artesunate, France, 2011–2013

Stéphane JauréguiberryComments to Author , Marc Thellier, Papa Alioune Ndour, Flavie Ader, Camille Roussel, Romain Sonneville, Julien Mayaux, Sophie Matheron, Adela Angoulvant, Benjamin Wyplosz, Christophe Rapp, Thierry Pistone, Bénédicte Lebrun-Vignes, Eric Kendjo, Martin Danis, Sandrine Houzé, François Bricaire, Dominique Mazier, Pierre Buffet, Eric Caumes, and French Artesunate Working Group
Author affiliations: Université Pierre et Marie Curie, Paris, France (S. Jauréguiberry, M. Thellier, P.A. Ndour, C. Roussel, M. Danis, D. Mazier, P. Buffet, E. Caumes)Hôpital Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris (APHP), Paris (S. Jauréguiberry, M. Thellier, F. Ader, J. Mayaux, B. Lebrun-Vignes, M. Danis, F. Bricaire, D. Mazier, P. Buffet, E. Caumes)Centre National de Référence du Paludisme, Paris (S. Jauréguiberry, M. Thellier, E. Kendjo, M. Danis, D. Mazier, P. Buffet)Hôpital Bichat, APHP, Paris (R. Sonneville, S. Matheron, S. Houzé);Université Paris-Sud, Orsay, France (A. Angoulvant)Hôpital de Bicêtre, Le Kremlin Bicêtre, APHP, France (A. Angoulvant, B. Wyplosz)Hôpital d’Instruction des Armées Begin, St. Mandé, France (C. Rapp)Hôpital Pellegrin, Bordeaux, France (T. Pistone)

Abstract

Artesunate is the most effective treatment for severe malaria. However, delayed-onset hemolytic anemia has been observed in ≈20% of travelers who receive artesunate, ≈60% of whom require transfusion. This finding could discourage physicians from using artesunate. We prospectively evaluated a cohort of 123 patients in France who had severe imported malaria that was treated with artesunate; our evaluation focused on outcome, adverse events, and postartesunate delayed-onset hemolysis (PADH). Of the 123 patients, 6 (5%) died. Overall, 97 adverse events occurred. Among the 78 patients who received follow-up for >8 days after treatment initiation, 76 (97%) had anemia, and 21 (27%) of the 78 cases were recorded as PADH. The median drop in hemoglobin levels was 1.3 g/dL; 15% of patients with PADH had hemoglobin levels of <7 g/dL, and 1 required transfusion. Despite the high incidence of PADH, the resulting anemia remained mild in 85% of cases. This reassuring result confirms the safety and therapeutic benefit of artesunate.
Intravenous (IV) artesunate has been the recommended first-line treatment for severe malaria worldwide since 2010 (1). Two large randomized trials showed a 35.0% reduction (from 22.0% to 15.0%) in death rates among adults in Asia and a 22.5% (from 10.9% to 8.5%) reduction among children in Africa when artesunate was compared with parenteral quinine in the treatment of severe malaria (2,3). Four case series performed in Western countries reported death rates of <4% (47).
Artesunate is generally considered safe (8). However, its use in Western countries has shown that delayed hemolytic events occur in ≈20% of patients with severe imported malaria, and 60% of these patients require blood transfusion (4,6,7,911). Delayed-onset anemia (herein referred to as postartesunate delayed-onset hemolysis [PADH] pattern of anemia) has been observed to occur 2–3 weeks after initiation of IV artesunate, after complete clearance of parasites, and to resolve during weeks 3–6 (7). The mechanism of this anemia is hemolytic, as demonstrated by high serum lactate dehydrogenase (LDH) and low plasma haptoglobin levels. Across several studies, no common conventional cause of hemolysis was identified (4,6,1214). In a comparative study, PADH anemia was described in 5 of 8 patients with hyperparasitemia treated with artesunate alone or combined with quinine; it was not seen in patients treated with quinine alone. This finding supports the assumption that this side effect is associated with artesunate (11). PADH anemia has not been reported in meta-analyses (8) nor observed in large clinical trials (2,3). However PADH has been reported recently in children in Africa (15).
This PADH is a matter of concern for the medical community. Without a systematic assessment of the incidence and outcome of artesunate-associated PADH anemia, a slowdown may occur in the ongoing change toward favoring treatment with artesunate rather than quinine, a less-efficient treatment for severe malaria. The World Health Organization recently recommended increased vigilance for PADH anemia and called for a more precise description of its incidence, time course, and severity (16). To determine the effectiveness and safety of artesunate in patients with severe imported malaria, we focused on PADH anemia cases detected through an existing artesunate surveillance program in France.

Dr. Jauréguiberry is a physician in the Department of Infectious and Tropical Diseases at the Pitié Salpêtrière University Hospital in Paris. His research interests include the pathophysiology and treatment of malaria and the epidemiology of imported diseases.

Acknowledgments


We thank Ipsita Sinha, Charlie Woodrow, and Muriel Vray for fruitful discussions. We are grateful to Elsa Boher and Françoise Mancel for constructive interactions.
This work was supported by grants from the Domaine d'Interêt Majeur Maladies Infectieuses Région Ile-de-France, the Worldwide Antimalarial Resistance Network Fast-Track Drugs & Biologics, LLC, the Bill and Melinda Gates Foundation, and the Follereau Foundation. Further support was provided by an Inserm-APHP France interface contract. S.J. has a grant from the Collège des Universitaires des Maladies Infectieuses et Tropicales.
S.J. and P.B. are engaged in a collaboration with Guilin Laboratories. P.B. provided expertise to Sigma-Tau Laboratories and Sanofi Aventis Group Research and Development. D.M., M.T., and T.P. provided expertise to Sigma-Tau Laboratories in France. M.D. has provided expertise to Sigma-Tau and Sanofi Laboratories.

References

  1. World Health Organization. The treatment of malaria, 2nd ed. Geneva: the Organization. 2010.
  2. Dondorp ANosten FStepniewska KDay NWhite NArtesunate versus quinine for treatment of severe falciparum malaria: a randomised trial.Lancet2005;366:71725DOIPubMed
  3. Dondorp AMFanello CIHendriksen ICGomes ESeni AChhaganlal KDArtesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet2010;376:164757DOIPubMed
  4. Kreeftmeijer-Vegter ARvan Genderen PJVisser LGBierman WFClerinx Jvan Veldhuizen CKTreatment outcome of intravenous artesunate in patients with severe malaria in the Netherlands and Belgium. Malar J2012;11:102DOIPubMed
  5. Mørch KStrand ØDunlop OBerg ALangeland NLeiva RASevere malaria and artesunate treatment, Norway. Emerg Infect Dis2008;14:18168.DOIPubMed
  6. Rolling TSchmiedel SWichmann DWittkopf DBurchard GDCramer JPPost-treatment haemolysis in severe imported malaria after intravenous artesunate: case report of three patients with hyperparasitaemia. Malar J2012;11:169DOIPubMed
  7. Zoller TJunghanss TKapaun AGjorup IRichter JHugo-Persson MIntravenous artesunate for severe malaria in travelers, Europe. Emerg Infect Dis2011;17:7717DOIPubMed
  8. Sinclair DDonegan SIsba RLalloo DGArtesunate versus quinine for treating severe malaria. Cochrane Database Syst Rev2012;6:CD005967.PubMed
  9. Itoda IYasunami TKikuchi KYamaura HTotsuka KYoshinaga KSevere falciparum malaria with prolonged hemolytic anemia after successful treatment with intravenous artesunate [in Japanese]Kansenshogaku Zasshi2002;76:6003DOIPubMed
  10. Medicines for Malaria Venture. Experts Group Meeting on delayed anaemia following treatment with injectable artesunate [2015 Mar 7].http://www.mmv.org/sites/default/files/uploads/docs/events/2013/InjectableArtesunateExpertGroupMeeting.pdf
  11. Rolling TWichmann DSchmiedel SBurchard GDKluge SCramer JPArtesunate versus quinine in the treatment of severe imported malaria: comparative analysis of adverse events focussing on delayed haemolysis. Malar J2013;12:241DOIPubMed
  12. Centers for Disease Control and PreventionPublished reports of delayed hemolytic anemia after treatment with artesunate for severe malaria—worldwide, 2010–2012. MMWR Morb Mortal Wkly Rep2013;62:58 .PubMed
  13. Caramello PBalbiano RDe Blasi TChiriotto MDeagostini MCalleri GSevere malaria, artesunate and haemolysis. J Antimicrob Chemother.2012;67:20534DOIPubMed
  14. Kano SArtemisinin-based combination therapies and their introduction in Japan. J Infect Chemother2010;16:37582DOIPubMed
  15. Rolling TAgbenyega TIssifou SAdegnika AASylverken JSpahlinger DDelayed hemolysis after treatment with parenteral artesunate in African children with severe malaria—a double-center prospective study. J Infect Dis2014;209:19218DOIPubMed
  16. World Health Organization. Global Malaria Programme. WHO information note on delayed haemolytic anaemia following treatment with artesunate: October 2013 [2015 Mar 7]. http://www.who.int/malaria/publications/atoz/who_note_delayed_haemolytic_anaemia_oct13.pdf?ua=1
  17. Seringe EThellier MFontanet ALegros FBouchaud OAncelle TSevere imported Plasmodium falciparum malaria, France, 1996–2003. Emerg Infect Dis2011;17:80713DOIPubMed
  18. Agence Nationale de Sécurité du Médicament. Protocole d’utilisation thérapeutique et de receuil d’informations Malacef® (artésunate) 60 mg, poudre et solvant pour solution injectable. Version 3; April 2013 [2015 Mar 7].http://ansm.sante.fr/var/ansm_site/storage/original/application/01d138a64031bcf9f37fa2737308caa5.pdf
  19. SPLIFManagement and prevention of imported Plasmodium falciparum malaria: recommendations for clinical practice 2007. (Revision 2007 of the 1999 consensus conference.) Short text. Med Mal Infect2008;38:5467DOIPubMed
  20. World Health OrganizationCommunicable Diseases Cluster. Severe falciparum malaria. Trans R Soc Trop Med Hyg2000;94(Suppl 1):190.DOIPubMed
  21. Haut Conseil de la Santé Publique. Place de l’artésunate injectable dans le traitement du paludisme grave de l’adulte et de l’enfant. [2015 Mar 7].http://www.hcsp.fr/explore.cgi/telecharger/hcspr20130201_palugraveartesunate.pdf
  22. Dournon NBuffet PCaumes EClair BJaureguiberry SArtesunate for severe acute Plasmodium falciparum infection in a patient with myasthenia gravis. Am J Trop Med Hyg2012;87:4356DOIPubMed
  23. Bruneel FTubach FCorne PMegarbane BMira JPPeytel ESevere imported falciparum malaria: a cohort study in 400 critically ill adults. PLoS ONE2010;5:e13236DOIPubMed
  24. Legros FBouchaud OAncelle TArnaud ACojean SLe Bras JRisk factors for imported fatal Plasmodium falciparum malaria, France, 1996–2003.Emerg Infect Dis2007;13:8838.PubMed
  25. Eder MFarne HCargill TAbbara ADavidson RN. Intravenous artesunate versus intravenous quinine in the treatment of severe falciparum malaria: a retrospective evaluation from a UK centre. Pathog Globl Health. 2012;106:181–7.
  26. Corpolongo ADe Nardo PGhirga PGentilotti EBellagamba RTommasi CHaemolytic anaemia in an HIV-infected patient with severe falciparum malaria after treatment with oral artemether–lumefantrine. Malar J2012;11:91DOIPubMed
  27. Angus BJChotivanich KUdomsangpetch RWhite NJIn vivo removal of malaria parasites from red blood cells without their destruction in acute falciparum malaria. Blood1997;90:203740 .PubMed
  28. Buffet PAMilon GBrousse VCorreas JMDousset BCouvelard AEx vivo perfusion of human spleens maintains clearing and processing functions.Blood2006;107:374552DOIPubMed
  29. Buffet PASafeukui IDeplaine GBrousse VPrendki VThellier MThe pathogenesis of Plasmodium falciparum malaria in humans: insights from splenic physiology. [PubMed ]Blood2011;117:38192DOIPubMed
  30. Chotivanich KUdomsangpetch RDondorp AWilliams TAngus BSimpson JAThe mechanisms of parasite clearance after antimalarial treatment of Plasmodium falciparum malaria. J Infect Dis2000;182:62933DOIPubMed
  31. Jauréguiberry SNdour PARoussel CAder FSafeukui INguyen MPostartesunate delayed hemolysis is a predictable event related to the lifesaving effect of artemisinins. Blood2014;124:16775DOIPubMed
  32. Hess KMGoad JAArguin PMIntravenous artesunate for the treatment of severe malaria. Ann Pharmacother2010;44:12508DOIPubMed
  33. Ribeiro IROlliaro PSafety of artemisinin and its derivatives. A review of published and unpublished clinical trials. Med Trop (Mars)1998;58:503.PubMed
  34. Rosenthal PJArtesunate for the treatment of severe falciparum malaria. N Engl J Med2008;358:182936DOIPubMed
  35. Maude RJPlewes KFaiz MAHanson JCharunwatthana PLee SJDoes artesunate prolong the electrocardiograph QT interval in patients with severe malaria? Am J Trop Med Hyg2009;80:12632 .PubMed
  36. Shanks GDFor severe malaria, artesunate is the answer. Lancet2010;376:16212DOIPubMed
  37. World Health OrganizationMalaria Policy Advisory Committee to the WHO: conclusions and recommendations of September 2012 meeting. Malar J2012;11:424DOIPubMed

Figures

Tables

Technical Appendix

Suggested citation for this article: Jauréguiberry S, Thellier M, Ndour PA, Ader F, Roussel C, Sonneville R, et al. Delayed-onset hemolytic anemia in patients with severe malaria treated with artesunate, France, 2011–2013. Emerg Infect Dis. 2015 May [date cited]. http://dx.doi.org/10.3201/eid2105.141171
DOI: 10.3201/eid2105.141171
1Members of the French Artesunate Working Group are listed in the Technical Appendix.

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