PMID- 33581690
OWN - NLM
STAT- MEDLINE
DCOM- 20211122
LR  - 20211122
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Linking)
VI  - 73
IP  - 10
DP  - 2021 Nov 16
TI  - Intravenous Artesunate for the Treatment of Severe Imported Malaria: 
      Implementation, Efficacy, and Safety in 1391 Patients.
PG  - 1795-1804
LID - 10.1093/cid/ciab133 [doi]
AB  - BACKGROUND: Intravenous artesunate is the World Health Organization-recommended 
      first-line treatment for severe malaria worldwide, but it is still not fully 
      licensed in Europe. Observational studies documenting its safety and efficacy in 
      imported malaria are thus essential. METHODS: We prospectively collected clinical 
      and epidemiological features of 1391 artesunate-treated patients among 110 
      participant centers during the first 7 years (2011-2017) of a national program 
      implemented by the French Drug Agency. RESULTS: Artesunate became the most 
      frequent treatment for severe malaria in France, rising from 9.9% in 2011 to 
      71.4% in 2017. Mortality was estimated at 4.1%. Treatment failure was recorded in 
      27 patients, but mutations in the Kelch-13 gene were not observed. Main reported 
      adverse events (AEs) were anemia (136 cases), cardiac events (24, including 20 
      episodes of conduction disorders and/or arrhythmia), and liver enzyme elevation 
      (23). Mortality and AEs were similar in the general population and in people with 
      human immunodeficiency virus, who were overweight, or were pregnant, but the only 
      pregnant woman treated in the first trimester experimented a hemorrhagic 
      miscarriage. The incidence of post-artesunate-delayed hemolysis (PADH) was 42.8% 
      when specifically assessed in a 98-patient subgroup, but was not associated with 
      fatal outcomes or sequelae. PADH was twice as frequent in patients of European 
      compared with African origin. CONCLUSIONS: Artesunate was rapidly deployed and 
      displayed a robust clinical benefit in patients with severe imported malaria, 
      despite a high frequency of mild to moderate PADH. Further explorations in the 
      context of importation should assess outcomes during the first trimester of 
      pregnancy and collect rare but potentially severe cardiac AEs.
CI  - (c) The Author(s) 2021. Published by Oxford University Press for the Infectious 
      Diseases Society of America. All rights reserved. For permissions, e-mail: 
      journals.permissions@oup.com.
FAU - Roussel, Camille
AU  - Roussel C
AD  - Biologie Integree du Globule Rouge, INSERM, Universite de Paris, Universite des 
      Antilles, Paris, France.
AD  - Institut National de la Transfusion Sanguine, Paris, France.
FAU - Ndour, Papa Alioune
AU  - Ndour PA
AD  - Biologie Integree du Globule Rouge, INSERM, Universite de Paris, Universite des 
      Antilles, Paris, France.
AD  - Institut National de la Transfusion Sanguine, Paris, France.
FAU - Kendjo, Eric
AU  - Kendjo E
AD  - Center National de Reference du Paludisme Paris, Paris, France.
AD  - Sorbonne Universite, INSERM, Institut Pierre-Louis d'Epidemiologie et de Sante 
      Publique, AP-HP, Hopital Pitie-Salpetriere, Paris, France.
FAU - Larreche, Sebastien
AU  - Larreche S
AD  - Departement de biologie medicale, Hopital d'Instruction Des Armees Begin, 
      Saint-Mande, France.
FAU - Taieb, Aida
AU  - Taieb A
AD  - Center National de Reference du Paludisme Paris, Paris, France.
FAU - Henry, Benoit
AU  - Henry B
AD  - Biologie Integree du Globule Rouge, INSERM, Universite de Paris, Universite des 
      Antilles, Paris, France.
AD  - Institut National de la Transfusion Sanguine, Paris, France.
AD  - Hopital Necker Enfants Malades, Service des maladies infectieuses et tropicales, 
      APHP, Center d'Infectiologie Necker-Pasteur, Institut Imagine, Paris, France.
FAU - Lebrun-Vignes, Benedicte
AU  - Lebrun-Vignes B
AD  - Center regional de Pharmacovigilance, Hopital Pitie Salpetriere, APHP, Paris, 
      France.
FAU - Chambrion, Charlotte
AU  - Chambrion C
AD  - Biologie Integree du Globule Rouge, INSERM, Universite de Paris, Universite des 
      Antilles, Paris, France.
AD  - Institut National de la Transfusion Sanguine, Paris, France.
FAU - Argy, Nicolas
AU  - Argy N
AD  - Center National de Reference du Paludisme Paris, Paris, France.
AD  - Universite de Paris, MERIT, IRD, Paris, France.
AD  - Laboratoire de parasitologie-mycologie, Hopital Bichat-Claude Bernard, APHP, 
      Paris, France.
FAU - Houze, Sandrine
AU  - Houze S
AD  - Center National de Reference du Paludisme Paris, Paris, France.
AD  - Universite de Paris, MERIT, IRD, Paris, France.
AD  - Laboratoire de parasitologie-mycologie, Hopital Bichat-Claude Bernard, APHP, 
      Paris, France.
FAU - Mouri, Oussama
AU  - Mouri O
AD  - Center National de Reference du Paludisme Paris, Paris, France.
AD  - Laboratoire de parasitologie-mycologie, Hopital Pitie Salpetriere, APHP, Paris, 
      France.
FAU - Courtin, David
AU  - Courtin D
AD  - Universite de Paris, MERIT, IRD, Paris, France.
FAU - Angoulvant, Adela
AU  - Angoulvant A
AD  - Laboratoire de Parasitologie-Mycologie, Hopital Bicetre, APHP, Kremlin Bicetre, 
      France.
AD  - GQE Le Moulon, INRA, CNRS, AgroParisTech, University Paris-Sud, Universite 
      Paris-Saclay, Orsay, France.
FAU - Delacour, Herve
AU  - Delacour H
AD  - Departement de biologie medicale, Hopital d'Instruction Des Armees Begin, 
      Saint-Mande, France.
FAU - Gay, Frederick
AU  - Gay F
AD  - Center National de Reference du Paludisme Paris, Paris, France.
AD  - Laboratoire de parasitologie-mycologie, Hopital Pitie Salpetriere, APHP, Paris, 
      France.
FAU - Siriez, Jean-Yves
AU  - Siriez JY
AD  - Service d'accueil des urgences pediatriques, Hopital Robert Debre, Paris, France.
FAU - Danis, Martin
AU  - Danis M
AD  - Center National de Reference du Paludisme Paris, Paris, France.
FAU - Bruneel, Fabrice
AU  - Bruneel F
AD  - Service de reanimation, Center Hospitalier de Versailles, Hopital Andre Mignot, 
      Le Chesnay, France.
FAU - Bouchaud, Olivier
AU  - Bouchaud O
AD  - Service des maladies infectieuses et tropicales, Hopital Avicenne, Bobigny, 
      France.
FAU - Caumes, Eric
AU  - Caumes E
AD  - Sorbonne Universite, INSERM, Institut Pierre-Louis d'Epidemiologie et de Sante 
      Publique, AP-HP, Hopital Pitie-Salpetriere, Paris, France.
AD  - Service des maladies infectieuses et tropicales, Hopital Pitie Salpetriere, APHP, 
      Paris, France.
AD  - Societe Francaise de Medecine des Voyages, Paris, France.
FAU - Piarroux, Renaud
AU  - Piarroux R
AD  - Center National de Reference du Paludisme Paris, Paris, France.
AD  - Sorbonne Universite, INSERM, Institut Pierre-Louis d'Epidemiologie et de Sante 
      Publique, AP-HP, Hopital Pitie-Salpetriere, Paris, France.
AD  - Laboratoire de parasitologie-mycologie, Hopital Pitie Salpetriere, APHP, Paris, 
      France.
FAU - Thellier, Marc
AU  - Thellier M
AD  - Center National de Reference du Paludisme Paris, Paris, France.
AD  - Sorbonne Universite, INSERM, Institut Pierre-Louis d'Epidemiologie et de Sante 
      Publique, AP-HP, Hopital Pitie-Salpetriere, Paris, France.
AD  - Laboratoire de parasitologie-mycologie, Hopital Pitie Salpetriere, APHP, Paris, 
      France.
FAU - Jaureguiberry, Stephane
AU  - Jaureguiberry S
AD  - Center National de Reference du Paludisme Paris, Paris, France.
AD  - Societe Francaise de Medecine des Voyages, Paris, France.
AD  - Service des maladies infectieuses et tropicales, Hopital Bicetre, APHP, Kremlin 
      Bicetre, France.
AD  - Universite de Paris Saclay, INSERM, CESP (Centre de Recherche en Epidemiologie et 
      Sante des Populations) Villejuif, France.
FAU - Buffet, Pierre
AU  - Buffet P
AD  - Biologie Integree du Globule Rouge, INSERM, Universite de Paris, Universite des 
      Antilles, Paris, France.
AD  - Institut National de la Transfusion Sanguine, Paris, France.
AD  - Center National de Reference du Paludisme Paris, Paris, France.
CN  - FRench Artesunate Working Group
LA  - eng
GR  - OPP1123683/Bill and Melinda Gates Foundation provided financial support/
GR  - ANR-11-LABX-0051/"Investissements d'Avenir"/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Antimalarials)
RN  - 0 (Artemisinins)
RN  - 60W3249T9M (Artesunate)
SB  - IM
MH  - *Antimalarials/adverse effects
MH  - *Artemisinins/therapeutic use
MH  - Artesunate/therapeutic use
MH  - Female
MH  - Hemolysis
MH  - Humans
MH  - *Malaria/drug therapy
MH  - *Malaria, Falciparum/drug therapy
MH  - Pregnancy
OTO - NOTNLM
OT  - artesunate
OT  - post-artesunate-delayed hemolysis
OT  - safety
OT  - severe malaria
EDAT- 2021/02/14 06:00
MHDA- 2021/11/23 06:00
CRDT- 2021/02/13 20:20
PHST- 2020/11/06 00:00 [received]
PHST- 2021/02/11 00:00 [accepted]
PHST- 2021/02/14 06:00 [pubmed]
PHST- 2021/11/23 06:00 [medline]
PHST- 2021/02/13 20:20 [entrez]
AID - 6134777 [pii]
AID - 10.1093/cid/ciab133 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2021 Nov 16;73(10):1795-1804. doi: 10.1093/cid/ciab133.