Laboratory Findings, Compassionate Use of Favipiravir, and Outcome in Patients With Ebola Virus Disease, Guinea, 2015-A Retrospective Observational Study.


Journal

The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675

Informations de publication

Date de publication:
19 06 2019
Historique:
received: 14 02 2019
accepted: 14 02 2019
pubmed: 23 2 2019
medline: 25 2 2020
entrez: 22 2 2019
Statut: ppublish

Résumé

In 2015, the laboratory at the Ebola treatment center in Coyah, Guinea, confirmed Ebola virus disease (EVD) in 286 patients. The cycle threshold (Ct) of an Ebola virus-specific reverse transcription-polymerase chain reaction assay and 13 blood chemistry parameters were measured on admission and during hospitalization. Favipiravir treatment was offered to patients with EVD on a compassionate-use basis. To reduce biases in the raw field data, we carefully selected 163 of 286 patients with EVD for a retrospective study to assess associations between potential risk factors, alterations in blood chemistry findings, favipiravir treatment, and outcome. The case-fatality rate in favipiravir-treated patients was lower than in untreated patients (42.5% [31 of 73] vs 57.8% [52 of 90]; P = .053 by univariate analysis). In multivariate regression analysis, a higher Ct and a younger age were associated with survival (P < .001), while favipiravir treatment showed no statistically significant effect (P = .11). However, Kaplan-Meier analysis indicated a longer survival time in the favipiravir-treated group (P = .015). The study also showed characteristic changes in blood chemistry findings in patients who died, compared with survivors. Consistent with the JIKI trial, this retrospective study revealed a trend toward improved survival in favipiravir- treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time.

Sections du résumé

BACKGROUND
In 2015, the laboratory at the Ebola treatment center in Coyah, Guinea, confirmed Ebola virus disease (EVD) in 286 patients. The cycle threshold (Ct) of an Ebola virus-specific reverse transcription-polymerase chain reaction assay and 13 blood chemistry parameters were measured on admission and during hospitalization. Favipiravir treatment was offered to patients with EVD on a compassionate-use basis.
METHODS
To reduce biases in the raw field data, we carefully selected 163 of 286 patients with EVD for a retrospective study to assess associations between potential risk factors, alterations in blood chemistry findings, favipiravir treatment, and outcome.
RESULTS
The case-fatality rate in favipiravir-treated patients was lower than in untreated patients (42.5% [31 of 73] vs 57.8% [52 of 90]; P = .053 by univariate analysis). In multivariate regression analysis, a higher Ct and a younger age were associated with survival (P < .001), while favipiravir treatment showed no statistically significant effect (P = .11). However, Kaplan-Meier analysis indicated a longer survival time in the favipiravir-treated group (P = .015). The study also showed characteristic changes in blood chemistry findings in patients who died, compared with survivors.
CONCLUSIONS
Consistent with the JIKI trial, this retrospective study revealed a trend toward improved survival in favipiravir- treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time.

Identifiants

pubmed: 30788508
pii: 5350975
doi: 10.1093/infdis/jiz078
pmc: PMC6581890
doi:

Substances chimiques

Amides 0
Antiviral Agents 0
Pyrazines 0
favipiravir EW5GL2X7E0

Types de publication

Journal Article Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

195-202

Subventions

Organisme : World Health Organization
ID : 001
Pays : International

Informations de copyright

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

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Auteurs

Romy Kerber (R)

Bernhard Nocht Institute for Tropical Medicine, Hamburg.
European Mobile Laboratory Consortium, Hamburg.
German Center for Infection Research, Braunschweig.

Eva Lorenz (E)

Bernhard Nocht Institute for Tropical Medicine, Hamburg.
German Center for Infection Research, Braunschweig.

Sophie Duraffour (S)

Bernhard Nocht Institute for Tropical Medicine, Hamburg.
European Mobile Laboratory Consortium, Hamburg.
German Center for Infection Research, Braunschweig.

Daouda Sissoko (D)

INSERM U1219, Bordeaux University, Bordeaux, France.
Bordeaux University Hospital, Bordeaux, France.

Martin Rudolf (M)

Bernhard Nocht Institute for Tropical Medicine, Hamburg.
European Mobile Laboratory Consortium, Hamburg.
German Center for Infection Research, Braunschweig.

Anna Jaeger (A)

Bernhard Nocht Institute for Tropical Medicine, Hamburg.
German Center for Infection Research, Braunschweig.

Sekou Ditinn Cisse (SD)

Ministry of Health Guinea, Guinea.

Alseny-Modet Camara (AM)

Ministry of Health Guinea, Guinea.

Osvaldo Miranda (O)

Hospital Militar Central Dr. Carlos J. Finlay, Havana, Cuba.

Carlos M Castro (CM)

Hospital Militar Central Dr. Carlos J. Finlay, Havana, Cuba.

Joseph Akoi Bore (J)

European Mobile Laboratory Consortium, Hamburg.
Ministry of Health Guinea, Guinea.

Fara Raymond Koundouno (F)

European Mobile Laboratory Consortium, Hamburg.
Ministry of Health Guinea, Guinea.

Johanna Repits (J)

European Mobile Laboratory Consortium, Hamburg.
Janssen-Cilag, Sollentuna, Sweden.

Babak Afrough (B)

European Mobile Laboratory Consortium, Hamburg.
Public Health England, Porton Down.

Beate Becker-Ziaja (B)

Bernhard Nocht Institute for Tropical Medicine, Hamburg.
European Mobile Laboratory Consortium, Hamburg.
German Center for Infection Research, Braunschweig.

Julia Hinzmann (J)

European Mobile Laboratory Consortium, Hamburg.
Robert Koch Institute, Berlin.

Marc Mertens (M)

European Mobile Laboratory Consortium, Hamburg.
German Center for Infection Research, Braunschweig.
Friedrich Loeffler Institute, Federal Research Institute for Animal Health, Greifswald.

Ines Vitoriano (I)

European Mobile Laboratory Consortium, Hamburg.
Public Health England, Porton Down.

Christopher Hugh Logue (C)

European Mobile Laboratory Consortium, Hamburg.
Public Health England, Porton Down.

Jan-Peter Böttcher (JP)

European Mobile Laboratory Consortium, Hamburg.
Robert Koch Institute, Berlin.

Elisa Pallasch (E)

Bernhard Nocht Institute for Tropical Medicine, Hamburg.
European Mobile Laboratory Consortium, Hamburg.
German Center for Infection Research, Braunschweig.

Andreas Sachse (A)

European Mobile Laboratory Consortium, Hamburg.
Robert Koch Institute, Berlin.

Amadou Bah (A)

European Mobile Laboratory Consortium, Hamburg.
Swiss Tropical and Public Health Institute, Basel.

Mar Cabeza-Cabrerizo (M)

European Mobile Laboratory Consortium, Hamburg.

Katja Nitzsche (K)

European Mobile Laboratory Consortium, Hamburg.

Eeva Kuisma (E)

European Mobile Laboratory Consortium, Hamburg.
Public Health England, Porton Down.

Janine Michel (J)

European Mobile Laboratory Consortium, Hamburg.
Robert Koch Institute, Berlin.

Tobias Holm (T)

Bernhard Nocht Institute for Tropical Medicine, Hamburg.
European Mobile Laboratory Consortium, Hamburg.
German Center for Infection Research, Braunschweig.

Elsa Gayle Zekeng (EG)

European Mobile Laboratory Consortium, Hamburg.

Lauren A Cowley (LA)

European Mobile Laboratory Consortium, Hamburg.
Public Health England, London.
Milner Centre for Evolution, University of Bath, Bath.

Isabel Garcia-Dorival (I)

European Mobile Laboratory Consortium, Hamburg.
Institute of Infection and Global Health, University of Liverpool, Liverpool.

Nicole Hetzelt (N)

European Mobile Laboratory Consortium, Hamburg.
Robert Koch Institute, Berlin.

Jonathan Hans Josef Baum (JHJ)

Bernhard Nocht Institute for Tropical Medicine, Hamburg.
European Mobile Laboratory Consortium, Hamburg.

Jasmine Portmann (J)

European Mobile Laboratory Consortium, Hamburg.
Federal Office for Civil Protection, Spiez Laboratory, Spiez.

Lisa Carter (L)

European Mobile Laboratory Consortium, Hamburg.
University College London, London.
World Health Organization, Geneva, Switzerland.

Rahel Lemma Yenamaberhan (RL)

Bernhard Nocht Institute for Tropical Medicine, Hamburg.
European Mobile Laboratory Consortium, Hamburg.

Alvaro Camino (A)

European Mobile Laboratory Consortium, Hamburg.

Theresa Enkirch (T)

European Mobile Laboratory Consortium, Hamburg.
Division of Veterinary Medicine, Paul-Ehrlich-Institut, Langen, Germany.

Katrin Singethan (K)

European Mobile Laboratory Consortium, Hamburg.
Institute of Virology, Technische Universität München, Munich, Germany.

Sarah Meisel (S)

Bernhard Nocht Institute for Tropical Medicine, Hamburg.
European Mobile Laboratory Consortium, Hamburg.

Antonio Mazzarelli (A)

European Mobile Laboratory Consortium, Hamburg.
National Institute for Infectious Diseases "Lazzaro Spallanzani," Rome, Italy.

Abigail Kosgei (A)

European Mobile Laboratory Consortium, Hamburg.
Kenya Medical Research Institute, Nairobi, Kenya.

Liana Kafetzopoulou (L)

European Mobile Laboratory Consortium, Hamburg.
KU Leuven-University of Leuven, Rega Institute for Medical Research, Leuven, Belgium.

Natasha Y Rickett (NY)

European Mobile Laboratory Consortium, Hamburg.
Institute of Infection and Global Health, University of Liverpool, Liverpool.

Livia Victoria Patrono (LV)

Bernhard Nocht Institute for Tropical Medicine, Hamburg.
European Mobile Laboratory Consortium, Hamburg.

Luam Ghebreghiorghis (L)

European Mobile Laboratory Consortium, Hamburg.
Robert Koch Institute, Berlin.

Ulrike Arnold (U)

European Mobile Laboratory Consortium, Hamburg.
Robert Koch Institute, Berlin.

Géraldine Colin (G)

INSERM U1219, Bordeaux University, Bordeaux, France.
Bordeaux University Hospital, Bordeaux, France.
PAC-CI, ANRS Research Site, Treichville University Hospital, Abidjan, Côte d'Ivoire.

Sylvain Juchet (S)

INSERM U1219, Bordeaux University, Bordeaux, France.
Bordeaux University Hospital, Bordeaux, France.
PAC-CI, ANRS Research Site, Treichville University Hospital, Abidjan, Côte d'Ivoire.

Claire Levy Marchal (CL)

INSERM U1219, Bordeaux University, Bordeaux, France.

Jacques Seraphin Kolie (JS)

Centre de Recherche en Santé Rurale, Maférinya, Guinea.

Abdoul Habib Beavogui (AH)

Centre de Recherche en Santé Rurale, Maférinya, Guinea.

Stephanie Wurr (S)

Bernhard Nocht Institute for Tropical Medicine, Hamburg.
European Mobile Laboratory Consortium, Hamburg.
German Center for Infection Research, Braunschweig.

Sabrina Bockholt (S)

Bernhard Nocht Institute for Tropical Medicine, Hamburg.
European Mobile Laboratory Consortium, Hamburg.
German Center for Infection Research, Braunschweig.

Ralf Krumkamp (R)

Bernhard Nocht Institute for Tropical Medicine, Hamburg.
German Center for Infection Research, Braunschweig.

Jürgen May (J)

Bernhard Nocht Institute for Tropical Medicine, Hamburg.
German Center for Infection Research, Braunschweig.

Kilian Stoecker (K)

European Mobile Laboratory Consortium, Hamburg.
German Center for Infection Research, Braunschweig.
Bundeswehr Institute of Microbiology, Munich, Germany.

Erna Fleischmann (E)

European Mobile Laboratory Consortium, Hamburg.
German Center for Infection Research, Braunschweig.
Bundeswehr Institute of Microbiology, Munich, Germany.

Giuseppe Ippolito (G)

European Mobile Laboratory Consortium, Hamburg.
National Institute for Infectious Diseases "Lazzaro Spallanzani," Rome, Italy.

Miles W Carroll (MW)

European Mobile Laboratory Consortium, Hamburg.
Public Health England, Porton Down.
University of Southampton, South General Hospital, Southampton, United Kingdom.

Lamine Koivogui (L)

Institut National de Santé Publique, Guinea.

N'Faly Magassouba (N)

Laboratoire des Fièvres Hémorragiques en Guinée, Université Gamal Abdel Nasser de Conakry, Guinea.

Sakoba Keita (S)

Ministry of Health Guinea, Guinea.

Céline Gurry (C)

World Health Organization, Geneva, Switzerland.

Patrick Drury (P)

World Health Organization, Geneva, Switzerland.

Boubacar Diallo (B)

World Health Organization, Conakry, Guinea.

Pierre Formenty (P)

World Health Organization, Geneva, Switzerland.

Roman Wölfel (R)

European Mobile Laboratory Consortium, Hamburg.
German Center for Infection Research, Braunschweig.
Bundeswehr Institute of Microbiology, Munich, Germany.

Antonino Di Caro (A)

European Mobile Laboratory Consortium, Hamburg.
National Institute for Infectious Diseases "Lazzaro Spallanzani," Rome, Italy.

Martin Gabriel (M)

Bernhard Nocht Institute for Tropical Medicine, Hamburg.
European Mobile Laboratory Consortium, Hamburg.
German Center for Infection Research, Braunschweig.

Xavier Anglaret (X)

INSERM U1219, Bordeaux University, Bordeaux, France.
Bordeaux University Hospital, Bordeaux, France.
PAC-CI, ANRS Research Site, Treichville University Hospital, Abidjan, Côte d'Ivoire.

Denis Malvy (D)

INSERM U1219, Bordeaux University, Bordeaux, France.
Bordeaux University Hospital, Bordeaux, France.

Stephan Günther (S)

Bernhard Nocht Institute for Tropical Medicine, Hamburg.
European Mobile Laboratory Consortium, Hamburg.
German Center for Infection Research, Braunschweig.

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