West Indies-French Guiana Dengue Study (DAG)

Dengue is a mosquito-born viral disease caused by four different serotypes of dengue virus (DENV). Dengue fever (DF) is defined by the sudden onset of fever associated with non specific constitutional symptoms, recovery occurring spontaneously after three to seven days. The infection can sometimes progress to dengue hemorrhagic fever (DHF), a disease characterized by a transient increase in vascular permeability provoking a plasma leakage syndrome. DHF can be complicated by shock and internal hemorrhage. Other rarer but potentially life-threatening complications include encephalitis, hepatitis, rhabdomyolysis, and myocarditis. There is currently no way of predicting the outcome of DF or DHF, and the World Health Organisation (WHO) classification lacks sufficient sensitivity and specificity to recognize and guide the management of severe forms of dengue. The pathophysiology of these severe forms is also poorly known, but it involves both host characteristics (immunological facilitation in case of new infection by a different serotype, and genetic factors), and viral factors. Dengue is an emerging disease in Asia and in South-America, with an exponential increase in the number of reported cases (50 to 100 million per year), the number of affected countries, and the number of severe cases. It affects both children and adults. Since the early 2000s, the French West Indies and French Guiana have become hyperendemic for dengue, with simultaneous circulation of the four serotypes, regular large outbreaks, and severe dengue including fatalities. This epidemiological situation calls for large prospective multicenter cohort studies to characterize severe forms of dengue, to seek predictive factors, and to investigate the pathophysiology of the disease (JL Deen Lancet 2006, A Kroeger Lancet 2006). The 2007-2008 West Indies- French Guiana French interministerial mission on emerging infectious diseases, coordinated by Professor Antoine Flahault, recommended such studies and underlined the excellent situation of Guyana for this type of study, and as an interface for clinical and basic research.

Principal objective To identify demographic, clinical, biological, virologic, immunologic and genetic factors associated with or predictive of severe complications of dengue fever (shock, internal bleeding, organ failure, death) in a cohort of children and adults with confirmed dengue fever, receiving early hospital care (within 96 hours following symptom onset) in French West Indies or French Guiana.

Secondary objective

1. To identify demographic, clinical, biological, virologic, immunologic and genetic factors associated with or predictive of dengue hemorrhagic fever (as defined by the World Health Organisation), and severe complications (shock, internal bleeding, organ failure, death) in the same cohort.
2. To identify demographic, clinical, biological, virologic, immunologic and genetic factors predictive of altered quality of life after the acute phase of dengue fever in the same cohort.

Hospital cohort of children and adults with suspected dengue fever in the French West Indies and French Guiana.

• Fever
• Dengue

• Other: biological sample collection
  blood sample collection
• Other: quality of life questionnaire EuroQol®
  Changes in quality of life, measured with the EuroQol® questionnaire 3 and 12 weeks after the onset of dengue fever symptoms.

Inclusion Criteria:

• Adult, and child aged at least 8 days and with weight >3 Kg
• Consulting a participating hospital center (emergency room, full hospitalization, day hospitalization, or outpatient visit).
• Clinical and biological signs of dengue fever on the day of enrollment or within the previous 96 hours, namely fever (documented, or reported by the patient or family) and two or more of the following signs: headache, rash, myalgia, arthralgia, abdominal pain, hemorrhage, and thrombocytopenia, and pain in children under 6 years, presence of pain greater than or equal to 4/10 on hetero assessment scale age age-appropriate
• Symptom onset less than 96 hours before the first hospital visit (enrollment visit).
• Possibility of follow-up throughout the 12-week study period.
• Patient or holder of parental authority registered in the French medical social security national program
• 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:

• Newborn less than 8 days old or with weight<3Kg
• Symptom onset more than 96 hours previously
• Clinical diagnosis of an infection other than dengue.
• Confirmed Malaria Access
• No follow-up possible after the first visit
• Refusal to participate in the study
• Patient or holder of parental authority not registered in the French medical social security national program
• Included patient and ongoing followed patient in the study

• Institut National de la Santé Et de la Recherche Médicale, France
• Centre d'Investigation Clinique - Epidémiologie Clinique CIE 802