REACTing methodology centre


In June 2013, under the aegis of the French Life Sciences and Healthcare Alliance (AVIESAN), France launched a consortium called REACTing: REsearch and ACTion targeting emerging infectious diseases. REACTing ( is coordinated by Prof. Yazdan Yazdanpanah (Lévy Y, Yazdanpanah Y, Delfraissy JF. Lancet 2016).

REACTing is a multidisciplinary approach bringing together excellent teams and laboratories, in order to prepare and coordinate research to deal with a threat that hasn’t happened yet and that is therefore, by definition, unforeseeable.

This consortium is organised around a steering committee of some fifteen human and animal health specialists; it relies on an 8-member scientific committee and a methodology centre. REACTing does not target any particular disease, and can get involved in all emerging infectious diseases. It has a broad scope, ranging from basic research to the human and social sciences, including environmental sciences, epidemiology and public health. The approach is broad-based and multidisciplinary, because we know that health crises are always complex phenomena in both their causes and their effects.

REACTing has two objectives:

  • To improve research planning during periods between crises (peace time): governance, preparation of research tools, identification of research priorities, application for funding, and preparation of ethical and legal aspects essential to preparing for research projects to be set up in an emergency ;
  • To coordinate, fund and establish research projects during periods of epidemic crisis: coordination, scientific and strategic priorities, methodological assistance, and informing the authorities and general public.

This consortium gained international visibility through its actions during the epidemic of Ebola and Zika, in particular (

REACTing Methodology Center

The REACTing Methodology Center is under the responsibility of Pr France Mentré (IAME UMRS 1137 & Département d’Epidémiologie, de Biostatistiques et Recherche Clinique – Hôpital Bichat, HUNPVS, AP-HP, Paris).

Staff of the REACTing Methodology Center

Name Expertise field
France MENTRE PU-PH Biostatistics Head of the Methodology Center
Cédric LAOUENAN MCU-PH Biostatistics Methodologist / statistician
Minerva CERVANTES GONZALEZ Physician-Virologist Clinical study physician
Isabelle HOFFMANN Clinical trials (regulatory aspect) Project Manager

Clinical trials in which the REACTing Methodology Center is involved (methodological and logistical support for the implementation, monitoring and analysis of projects)


CARBO cohort of patients suffering acute arbovirus infection (Pr André Cabié, sponsor: CHU Fort de France).

This cohort allows to follow and characterize diseases such as Dengue, Chikungunya and Zika virus infection and any other arbovirus that might emerge in the West Indies (Guadeloupe and Martinique), French Guiana (Cayenne) or Metropolitan France.

ARBHITA (Dr Sylvie Abel, sponsor: CHU Fort de France) is an ancillary study of CARBO whose methodology and statistical analyzes are under the responsibility of REACTing Methodology Center.

The aim of this study is to describe precisely the natural history of arbovirus infection by analyzing the evolution of several biomarkers in a limited number of patients included in the CARBO cohort.

The data collected have great scientific value (description of viral kinetics and antibodies and establishes a very complete biological collection: venous and capillary blood, urine, stools, tears, pharyngeal secretions, saliva, sperm, vaginal secretions, milk).

CHIKIVIG-01 (Pr Bruno Hoen, sponsor: CHU Pointe à Pitre) is a therapeutic trial (« Prevention of Chikungunya Infection in Neonates: Clinical Evaluation of Anti-CHIKV Hyperimmune Intravenous Immunoglobulins »).

The investigators hypothesize that the administration of anti-CHIKV hyperimmune human intravenous immunoglobulins to neonates exposed to a high risk of severe form of Chikungunya infection is safe enough to justify its evaluation in an open non randomized trial aimed to confirm the safety and preliminary assess the efficacy of this intervention.

ZIKA-DFA (Pr Bruno Hoen, CHU Pointe à Pitre, sponsor: INSERM)

The Zika epidemic has spread into the three French Overseas Departments in the Caribbean (DFAs) in 2016.

This prospective observational, non-interventional study is meant to collect, within usual care practices, clinical and paraclinical information which will allow the precise description of the consequences of ZIKV infection occurring during pregnancy.

This study has 2 arms:

  • Zika Virus Infection’s Neonatal and Pediatric Consequences in French Department of America (ZIKA-DFA-BB)
  • Zika Virus Infection’s Pregnancy Consequences in French Department of America (ZIKA-DFA-FE)



II) EBOLA projects

JIKI trial (Pr Denis Malvy, CHU Bordeaux, sponsor: INSERM) «Efficacy of Favipiravir in Reducing Mortality in Individuals With Ebola Virus Disease in Guinea ».

The REACTing Methodology Center collaborated with a team of researchers in Bordeaux to develop and implement the JIKI trial. The REACTing Methodology Center was responsible for the statistical analyzes. The results were published « Experimental Treatment with Favipiravir for Ebola Virus diseases (the JIKI Trial): A Historically controlled, single-arm proof-of- Concept Trial in Guinea » Plos Med ; Mars 2016. These first results open up possibilities in the treatment of this disease.

FORCE trial (Dr Daouda Sissoko, CHU Bordeaux, sponsor: INSERM) «Tolerance and Activity Evaluation of High Doses of Favipiravir Against Ebola Virus in the Semen ».

This study aims to evaluate favipiravir high dose tolerance in male survivor of Ebola Virus Disease (EVD) with Ebola Virus (EBOV) RNA in semen. This is a dose escalation study with 3 cohorts of 6 patients, each dose level including 2 sentinel patients.

The REACTing Methodology Center was responsible for the statistical analyzes.

Publications associated with REACTing activities

Stegmann-Planchard S, Gallian P, Tressières B, Leparc-Goffart I, Lannuzel A, Signaté A, Laouénan C, Cabié A, Hoen B. Chikungunya, a risk factor for Guillain-Barré syndrome. Clin Infect Dis. 9 juill 2019;
Cousien A, Abel S, Monthieux A, Andronico A, Calmont I, Cervantes M, Césaire R, Gallian P, de Lamballerie X, Laouénan C, Najioullah F, Pierre-François S, Pircher M, Salje H, Ten Bosch QA, Cabié A, Cauchemez S. Assessing Zika Virus Transmission within Households during an Outbreak in Martinique, 2015-2016. Am J Epidemiol. 17 avr 2019;
Reynard S, Journeaux A, Gloaguen E, Schaeffer J, Varet H, Pietrosemoli N, Mateo M, Baillet N, Laouenan C, Raoul H, Mullaert J, Baize S. Immune parameters and outcomes during Ebola virus disease. JCI Insight. 10 janv 2019;4(1).
Madelain V, Baize S, Jacquot F, Reynard S, Fizet A, Barron S, Solas C, Lacarelle B, Carbonnelle C, Mentré F, Raoul H, de Lamballerie X, Guedj J. Ebola viral dynamics in nonhuman primates provides insights into virus immuno-pathogenesis and antiviral strategies. Nat Commun. 01 2018;9(1):4013.
Hoen B, Schaub B, Funk AL, Ardillon V, Boullard M, Cabié A, Callier C, Carles G, Cassadou S, Césaire R, Douine M, Herrmann-Storck C, Kadhel P, Laouénan C, Madec Y, Monthieux A, Nacher M, Najioullah F, Rousset D, Ryan C, Schepers K, Stegmann-Planchard S, Tressières B, Voluménie J-L, Yassinguezo S, Janky E, Fontanet A. Pregnancy Outcomes after ZIKV Infection in French Territories in the Americas. N Engl J Med. 15 2018;378(11):985‑94.
Guedj J, Piorkowski G, Jacquot F, Madelain V, Nguyen THT, Rodallec A, Gunther S, Carbonnelle C, Mentré F, Raoul H, de Lamballerie X. Antiviral efficacy of favipiravir against Ebola virus: A translational study in cynomolgus macaques. PLoS Med. 2018;15(3):e1002535.
Best K, Guedj J, Madelain V, de Lamballerie X, Lim S-Y, Osuna CE, Whitney JB, Perelson AS. Zika plasma viral dynamics in nonhuman primates provides insights into early infection and antiviral strategies. Proceedings of the National Academy of Sciences of the United States of America. août 2017;114(33):8847–8852.
Nguyen THT, Guedj J, Anglaret X, Laouénan C, Madelain V, Taburet A-M, Baize S, Sissoko D, Pastorino B, Rodallec A, Piorkowski G, Carazo S, Conde MN, Gala J-L, Bore JA, Carbonnelle C, Jacquot F, Raoul H, Malvy D, de Lamballerie X, Mentré F, JIKI study group. Favipiravir pharmacokinetics in Ebola-Infected patients of the JIKI trial reveals concentrations lower than targeted. PLoS neglected tropical diseases. févr 2017;11(2):e0005389.
Madelain V, Guedj J, Mentré F, Nguyen THT, Jacquot F, Oestereich L, Kadota T, Yamada K, Taburet A-M, de Lamballerie X, Raoul H. Favipiravir Pharmacokinetics in Nonhuman Primates and Insights for Future Efficacy Studies of Hemorrhagic Fever Viruses. Antimicrob Agents Chemother. janv 2017;61(1).
Madelain V, Nguyen THT, Olivo A, de Lamballerie X, Guedj J, Taburet A-M, Mentré F. Ebola Virus Infection: Review of the Pharmacokinetic and Pharmacodynamic Properties of Drugs Considered for Testing in Human Efficacy Trials. Clin Pharmacokinet. août 2016;55(8):907‑23.
Delfraissy J-F, Yazdanpanah Y, Levy Y. REACTing: the French response to infectious disease crises. Lancet. 28 mai 2016;387(10034):2183‑5.
Sissoko D, Laouenan C, Folkesson E, M’Lebing A-B, Beavogui A-H, Baize S, Camara A-M, Maes P, Shepherd S, Danel C, Carazo S, Conde MN, Gala J-L, Colin G, Savini H, Bore JA, Le Marcis F, Koundouno FR, Petitjean F, Lamah M-C, Diederich S, Tounkara A, Poelart G, Berbain E, Dindart J-M, Duraffour S, Lefevre A, Leno T, Peyrouset O, Irenge L, Bangoura N, Palich R, Hinzmann J, Kraus A, Barry TS, Berette S, Bongono A, Camara MS, Chanfreau Munoz V, Doumbouya L, Souley Harouna null, Kighoma PM, Koundouno FR, Réné Lolamou null, Loua CM, Massala V, Moumouni K, Provost C, Samake N, Sekou C, Soumah A, Arnould I, Komano MS, Gustin L, Berutto C, Camara D, Camara FS, Colpaert J, Delamou L, Jansson L, Kourouma E, Loua M, Malme K, Manfrin E, Maomou A, Milinouno A, Ombelet S, Sidiboun AY, Verreckt I, Yombouno P, Bocquin A, Carbonnelle C, Carmoi T, Frange P, Mely S, Nguyen V-K, Pannetier D, Taburet A-M, Treluyer J-M, Kolie J, Moh R, Gonzalez MC, Kuisma E, Liedigk B, Ngabo D, Rudolf M, Thom R, Kerber R, Gabriel M, Di Caro A, Wölfel R, Badir J, Bentahir M, Deccache Y, Dumont C, Durant J-F, El Bakkouri K, Gasasira Uwamahoro M, Smits B, Toufik N, Van Cauwenberghe S, Ezzedine K, Dortenzio E, Pizarro L, Etienne A, Guedj J, Fizet A, Barte de Sainte Fare E, Murgue B, Tran-Minh T, Rapp C, Piguet P, Poncin M, Draguez B, Allaford Duverger T, Barbe S, Baret G, Defourny I, Carroll M, Raoul H, Augier A, Eholie SP, Yazdanpanah Y, Levy-Marchal C, Antierrens A, Van Herp M, Günther S, de Lamballerie X, Keïta S, Mentre F, Anglaret X, Malvy D, JIKI Study Group. Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea. PLoS Med. mars 2016;13(3):e1001967.
Yazdanpanah Y, Horby P, van Griensven J, Mentre F, Nguyen V-K, Malvy JMD, Dunning J, Sissoko D, Delfraissy J-F, Levy Y. Drug assessment in the Ebola virus disease epidemic in west Africa. Lancet Infect Dis. nov 2015;15(11):1258.
Madelain V, Oestereich L, Graw F, Nguyen THT, de Lamballerie X, Mentré F, Günther S, Guedj J. Ebola virus dynamics in mice treated with favipiravir. Antiviral Res. 2 sept 2015;123:70‑7.
Bouazza N, Treluyer J-M, Foissac F, Mentré F, Taburet A-M, Guedj J, Anglaret X, de Lamballerie X, Keïta S, Malvy D, Frange P. Favipiravir for children with Ebola. Lancet. 14 févr 2015;385(9968):603‑4.
Mentré F, Taburet A-M, Guedj J, Anglaret X, Keïta S, de Lamballerie X, Malvy D. Dose regimen of favipiravir for Ebola virus disease. Lancet Infect Dis. févr 2015;15(2):150‑1.