title: Postartesunate delayed hemolysis is a predictable event related to the lifesaving effect of artemisinins.
abstract: Patients with severe malaria treated with artesunate sometimes experience a delayed hemolytic episode. Artesunate (AS) induces pitting, a splenic process whereby dead parasites are expelled from their host erythrocytes. These once-infected erythrocytes then return to the circulation. We analyzed hematologic parameters in 123 travelers treated with AS for severe malaria. Among 60 nontransfused patients observed for more than 8 days, 13 (22%) had delayed hemolysis. The peak concentration of circulating once-infected erythrocytes was measured during the first week in 21 patients and was significantly higher in 9 patients with delayed hemolysis than in 12 with other patterns of anemia (0.30 vs 0.07; P = .0001). The threshold of 180 million once-infected erythrocytes per liter discriminated patients with delayed hemolysis with 89% sensitivity and 83% specificity. Once-infected erythrocyte morphology analyzed by using ImageStream in 4 patients showed an 8.9% reduction in their projected area, an alteration likely contributing to their shorter lifespan. Delayed clearance of infected erythrocytes spared by pitting during AS treatment is an original mechanism of hemolytic anemia. Our findings consolidate a disease framework for posttreatment anemia in malaria in which delayed hemolysis is a new entity. The early concentration of once-infected erythrocytes is a solid candidate marker to predict post-AS delayed hemolysis.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Service des Maladies Infectieuses et Médecine Tropicale, Paris, France; Centre d'Immunologie et des Maladies Infectieuses de Paris, U 1135 INSERM/Université Pierre et Marie Curie - Paris 6, Paris, France; Centre National de Référence du Paludisme-site Pitié Salpêtrière, Paris, France;
authors.forename: Stéphane
authors.initials: S
authors.lastname: Jauréguiberry
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses de Paris, U 1135 INSERM/Université Pierre et Marie Curie - Paris 6, Paris, France;
authors.forename: Papa A
authors.initials: PA
authors.lastname: Ndour
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses de Paris, U 1135 INSERM/Université Pierre et Marie Curie - Paris 6, Paris, France;
authors.forename: Camille
authors.initials: C
authors.lastname: Roussel
authors.affiliation: Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Service de Parasitologie, Paris, France;
authors.forename: Flavie
authors.initials: F
authors.lastname: Ader
authors.affiliation: Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN;
authors.forename: Innocent
authors.initials: I
authors.lastname: Safeukui
authors.affiliation: Institut Pasteur, Plate-forme de Cytométrie, Imagopole, Paris, France;
authors.forename: Marie
authors.initials: M
authors.lastname: Nguyen
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses de Paris, U 1135 INSERM/Université Pierre et Marie Curie - Paris 6, Paris, France;
authors.forename: Sylvestre
authors.initials: S
authors.lastname: Biligui
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses de Paris, U 1135 INSERM/Université Pierre et Marie Curie - Paris 6, Paris, France;
authors.forename: Liliane
authors.initials: L
authors.lastname: Ciceron
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses de Paris, U 1135 INSERM/Université Pierre et Marie Curie - Paris 6, Paris, France;
authors.forename: Oussama
authors.initials: O
authors.lastname: Mouri
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses de Paris, U 1135 INSERM/Université Pierre et Marie Curie - Paris 6, Paris, France; Centre National de Référence du Paludisme-site Pitié Salpêtrière, Paris, France;
authors.forename: Eric
authors.initials: E
authors.lastname: Kendjo
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Service des Maladies Infectieuses et Médecine Tropicale, Paris, France;
authors.forename: François
authors.initials: F
authors.lastname: Bricaire
authors.affiliation: Institut Pasteur, Unité d'Épidémiologie des Maladies Émergentes, Paris, France;
authors.forename: Muriel
authors.initials: M
authors.lastname: Vray
authors.affiliation: Assistance Publique - Hôpitaux de Paris, Hôpital de Bicêtre, Service de Parasitologie, Paris, France;
authors.forename: Adéla
authors.initials: A
authors.lastname: Angoulvant
authors.affiliation: Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Service de Réanimation Médicale, Paris, France; and.
authors.forename: Julien
authors.initials: J
authors.lastname: Mayaux
authors.affiliation: Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN;
authors.forename: Kasturi
authors.initials: K
authors.lastname: Haldar
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses de Paris, U 1135 INSERM/Université Pierre et Marie Curie - Paris 6, Paris, France; Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Service de Parasitologie, Paris, France;
authors.forename: Dominique
authors.initials: D
authors.lastname: Mazier
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses de Paris, U 1135 INSERM/Université Pierre et Marie Curie - Paris 6, Paris, France; Centre National de Référence du Paludisme-site Pitié Salpêtrière, Paris, France; Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Service de Parasitologie, Paris, France;
authors.forename: Martin
authors.initials: M
authors.lastname: Danis
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Service des Maladies Infectieuses et Médecine Tropicale, Paris, France;
authors.forename: Eric
authors.initials: E
authors.lastname: Caumes
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses de Paris, U 1135 INSERM/Université Pierre et Marie Curie - Paris 6, Paris, France; Centre National de Référence du Paludisme-site Pitié Salpêtrière, Paris, France; Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Service de Parasitologie, Paris, France;
authors.forename: Marc
authors.initials: M
authors.lastname: Thellier
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses de Paris, U 1135 INSERM/Université Pierre et Marie Curie - Paris 6, Paris, France; Centre National de Référence du Paludisme-site Pitié Salpêtrière, Paris, France; Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Service de Parasitologie, Paris, France; Laboratory of Excellence GRex.
authors.forename: Pierre
authors.initials: P
authors.lastname: Buffet
mesh_terms: D000328:Adult; D000743:Anemia, Hemolytic / Q000139:chemically induced / Q000469:parasitology; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D005260:Female; D005500:Follow-Up Studies; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D016778:Malaria, Falciparum / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate