Cohort of Patients Infected by an Arbovirus (CARBO)

Descriptive and Prognostic Study of Arbovirus Infections in France, Based on a Hospital Cohort of Children and Adults With Suspected Arbovirose.

There are hundred of arbovirus which have been shown to cause disease in humans. Their most common clinical symptoms are algo-eruptive (dengue, chikungunya, zika), hemorrhagic fever (dengue, yellow fever, Crimean-Congo hemorrhagic fever), neurological (West Nile, Zika, dengue, Japanese encephalitis) or arthritic afflictions (Chikungunya, O'nyong nyong). Dengue is a mosquito-born viral disease caused by 4 different serotypes of virus. Dengue fever (DF) is defined by the sudden onset of fever with non-specific constitutional symptoms, recovery occurring spontaneously in 3 to 7 days. The infection can sometimes progress to dengue hemorrhagic fever (DHF) characterized by a transient increase in vascular permeability provoking a plasma leakage syndrome. DHF can be complicated by shock and internal hemorrhage. Other rarer complications include encephalitis, hepatitis, rhabdomyolysis and myocarditis. There is currently no way of predicting the outcome of DF or DHF and the WHO classification lacks sufficient sensitivity and specificity to recognize and guide the management of severe forms of dengue. The pathophysiology of these forms is also poorly known. Since 2000s, the French West Indies and Guiana have become hyperendemic for dengue with simultaneous circulation of the 4 serotypes, regular large outbreaks and severe dengue including fatalities. Chikungunya is a re-emerging virus causing massive epidemics in Africa, in the Indian Ocean and Southeast Asia. The first autochthonous cases were described in French Antilles in Nov 2013. The disease typically consists of an acute illness like dengue fever with abrupt onset of a high-grade fever followed by constitutionals symptoms, poly-arthritis and skin involvement. Usually, the illness resolves in 4 to 6 weeks. However, severe clinical forms in early stage may appear and chronic clinical forms as incapacitating arthralgia which affect 40 to 60% of patients. In France, others arboviruses may cause severe emerging and re-emerging infectious diseases like Zika or West Nile. In non-immunized population these emerging diseases may cause outbreaks with specific severe clinical complications. The French interministerial mission on emerging infectious diseases coordinated by Professor Antoine Flahault, recommended such studies: large prospective multicenter cohort studies to characterize severe forms of arbovirus infections to seek predictive factors and to investigate the pathophysiology of the diseases.

Study Overview

• Status: Recruiting
• Conditions: Fever; Dengue; Chikungunya; Zika Virus
• Intervention / Treatment: Other: biological sample collection; Other: Quality of life Questionnaire EuroQol®; Other: Health Assessment Questionnaire - MDHAQ and RAPID3; Other: Neuropathic Pain Questionnaire (DN4)

Detailed Description

Principal objective To identify demographic, clinical, biological, virologic, immunologic and genetic factors associated with or predictive of severe complications of arbovirus infections (shock, internal bleeding, organ failure, death) in a cohort of children and adults with confirmed arbovirus infections, in France.

Secondary objective

To identify demographic, clinical, biological, virologic, immunologic and genetic factors predictive of altered quality of life after confirmed an acute arbovirus infection. Onset of specific complications:

• Hemorrhagic fever (dengue: WHO criteria)
• Neurological disorders (West Nile virus infection, Zika virus infection, Japanese encephalitis…)
• Chronic chikungunya (persistent Chronic chikungunya (persistent musculoskeletal symptoms for more than three months after symptoms onset)

• Study Type: Observational
• Enrollment (Anticipated): 1377

Contacts and Locations

• Study Contact: Name: Andre Cabie; Phone Number: 0596552301; Email: andre.cabie@chu-fortdefrance.fr

Study Locations

• France
  • Bordeaux, France, 33000
    • Recruiting
    • Hopital Saint André
    • Contact: Jean-Marie Denis MALVY; Phone Number: 05.57.82.22.20; Email: denis.malvy@chu-bordeaux.fr
  • Paris, France, 75018
    • Recruiting
    • Hopital Bichat-Claude Bernard
    • Contact: Sophie MATHERON, MD; Phone Number: 01 40 25 78 83; Email: Sophie.matheron@bch.ah-hop-paris.fr
  • Paris, France, 75013
    • Active, not recruiting
    • Hôpital La Pitié Salpêtrière
• French Guiana
  • Cayenne, French Guiana, 97300
    • Recruiting
    • CH André Rosemond
    • Contact: Félix Djossou, MD; Email: felix.djossou@ch-cayenne.fr
    • Principal Investigator: Félix Djossou, MD
• Guadeloupe
  • Pointe à Pitre, Guadeloupe, 97261
    • Recruiting
    • CHU de Pointe à Pitre/Abymes
    • Contact: Adeline MALLARD; Phone Number: 05 90 89 10 10; Email: adeline.mallard@chu-guadeloupe.fr
• Martinique
  • Fort-de-France, Martinique, 97200
    • Recruiting
    • Centre Hospitalier Universitaire de Martinique
    • Contact: Janick Jean-Marie; Phone Number: 0596 592697; Email: janick.jean-marie@chu-martinique.fr
    • Contact: Isabelle Calmont; Phone Number: 0596 592697; Email: isabelle.calmont@chu-martinique.fr
    • Principal Investigator: André CABIE, MD
• Réunion
  • Saint-Denis, Réunion, 97448
    • Recruiting
    • CHU de la réunion
    • Contact: Antoine BERTOLOTTI; Phone Number: 02 62 35 91 65; Email: antoine_bertolotti@yahoo.fr
  • Saint-Paul, Réunion, 97866
    • Recruiting
    • Centre Hospitalier Gabriel Martin
    • Contact: Rémi GIRERD; Phone Number: 0262453030; Email: remigirerd@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 week and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Hospital cohort of children and adults with suspected of infectious by an arbovirus in the overseas departments and regions and in France.

Description

INCLUSION CRITERIA :

• Adult, child or newborn with a weight > 2.5 kg the days of enrollment.
• Consulting a participating hospital center (emergency room, full hospitalization, day hospitalization, or outpatient visit).

• Arbovirosis suspected or confirmed biologically: A suspected case of arbovirus infection is defined by:

  • The combination of clinical and biological signs observed suggestive of arbovirosus infection: fever (reported by the patient or family, or documented), headache, rash, myalgia, arthralgia, abdominal pain, hemorrhage, thrombocytopenia, or
  • Children under 6 years: the report (by family or documented) of a fever on the day of enrollment or within 7 previous days, possibly accompanied by a of pain - At a patient with a notion of stay in 2 weeks preceding in a zone of arbovirus circulation (only for the imported cases)

A case of arbovirus infection confirmed biologically is defined by:

• RT-PCR arbovirus positive in plasma or urine (Zika virus infection), or by detection of the NS1 antigen (dengue), or an appearance or an significant increase (multiplication of the title by four) of the G immunoglobulin directed against arbovirus in question on an early taken serum (during the first week following the start of symptoms) and another taken at least 10 days later.
• Symptom onset within the 7 days before the enrollment visit or within 21 days for severe forms of the disease.Possibility of follow-up throughout study period. * Acceptance to participate in the study and in follow-up; informed consent of the patient (adult and minor in age to express his desire) or a legal representative (for minors, and patients unable to sign the consent form).

EXCLUSION CRITERIA :

• No follow-up possible after the first visit
• Patient or holder of parental authority not registered in the French medical social security national program

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence, during follow-up (for 12 weeks following symptom onset), of shock, internal bleeding, failure of one or several organs or systems (brain, heart, lung, liver, kidney, clotting system), or death.	The primary endpoint is a composite endpoint defined as the occurrence, within 12 weeks of the onset of arbovirosis, of at least 1 of the following events: death or shock or internal bleeding, or failure to one or more organs or systems (brain, heart, lung, liver, kidney, hemostasis). Deaths not attributable directly or indirectly to the arbovirosis in question will not be taken into account.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Specific complications: Onset of hemorrhagic fever (dengue) Onset of encephalitis or neurological disorders (West Nile virus, Japanese encephalitis, Zika virus) Onset of chronic form (Chikungunya)	The analysis will focus only on patients with biologically confirmed arbovirosis by one of the following exams: RT-PCR plasma (arbovirus), or urine (Zika virus),; Research of the NS1 positive antigen (dengue),; Significant appearance or increase of the G immunoglobulin directed against the arbovirus in question between an early serum (during the first week following the onset of symptoms) and another taken at least 10 days later	12 weeks

Collaborators and Investigators

• Sponsor: University Hospital Center of Martinique
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; Clinique Antilles-Guyane
• Investigators: Principal Investigator: Andre Cabie, MD, CHU de Martinique

Publications and helpful links

General Publications

• Bertolotti A, Thioune M, Abel S, Belrose G, Calmont I, Cesaire R, Cervantes M, Fagour L, Javelle E, Lebris C, Najioullah F, Pierre-Francois S, Roze B, Vigan M, Laouenan C, Cabie A; Chronic Chikungunya working group of University Medical Center of Martinique. Prevalence of chronic chikungunya and associated risks factors in the French West Indies (La Martinique): A prospective cohort study. PLoS Negl Trop Dis. 2020 Mar 12;14(3):e0007327. doi: 10.1371/journal.pntd.0007327. eCollection 2020 Mar.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2010
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: February 23, 2010
• First Submitted That Met QC Criteria: April 6, 2010
• First Posted (Estimate): April 8, 2010

Study Record Updates

• Last Update Posted (Actual): March 16, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: fever; Joint pain; dengue; dengue hemorrhagic fever; dengue virus; Chikungunya virus; Zika Virus
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Alphavirus Infections; Togaviridae Infections; Dengue; Chikungunya Fever; Zika Virus Infection
• Other Study ID Numbers: 09/B/08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED