Study to Evaluate the Incidence, Clinical Characteristics and Economic Burden of Dengue in Brazilian Children

Not Applicable

Completed

Conditions: Dengue

Interventions: Other: Data collection
Procedure: Blood sample collection

Registration Number: NCT01391819

Lead Sponsor: GlaxoSmithKline

Brief Summary: The aim of this study is to establish an active surveillance in order to generate dengue disease burden estimates including incidence rates, prevalence data, clinical presentation and cost of illness in Forteleza (Brazil).

Detailed Description: Prospective cohort study.

The study period initially planned to be two years, is extended by one year to cover one additional dengue season.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 2117

Inclusion Criteria

Male or female between 5 and 13 years of age (including children at least 5 years of age and excluding children who reached their fourteenth birthday) at the time of enrollment.
Written informed consent (and assent when applicable).
Subjects who the investigator believes that they and/or their parent(s)/LAR can and will comply with the requirements of the protocol (e.g. willingness to do a hospital visit in case of dengue suspicion, willingness to attend the study hospital return for follow-up visits, able to observe for signs of dengue, understand how to take a temperature, etc).
Subjects who plan to attend one of the study schools for two school years following enrollment.

Exclusion Criteria

Subjects planning to move from the study area during the two school years following enrollment.
Child in care.
Enrollment in another study that would conflict with the current study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Study cohort	Blood sample collection	Children age 5 to 13 years at the time of enrollment, selected from schools in Fortaleza.
Study cohort	Data collection	Children age 5 to 13 years at the time of enrollment, selected from schools in Fortaleza.

Primary Outcome Measures

Name	Time	Method
Incidence of All Laboratory-confirmed Symptomatic Dengue Infection	At Year 3 (2014)	Laboratory-confirmed dengue infection refers to suspected symptomatic dengue cases with positive dengue virus identification or serologic evidence of dengue infection through dengue virus identification through Reverse Transcriptase quantitative Polymerase Chain Reaction (RT-qPCR) from first blood sample or anti-dengue Immunoglobulin type M/G (IgM/G) seroconversions between first and second blood sampling. Note: In the study report the denominator for incidence estimation has not been expressed as an absolute number of subjects, but in person-years. Therefore, the category "number of subjects analysed" has been populated with the number of enrolled subjects attended the study visit after the specified season and in each age stratum.

Secondary Outcome Measures

Name	Time	Method
Number of Dengue Infection Cases by Virus Type (DENV)	From Day 0 to Year 3	Among virus types causing dengue infection were DENV-4 in 2012 and 2013 and DENV-1 in 2014, as assessed by PCR.
Number of Working Days Missed of Primary Care Giver 2 of Subjects With Laboratory Confirmed Symptomatic Dengue Cases	From 21 up to 35 days post laboratory confirmed dengue onset	The number of days off work from caregiver were recorded as part of health economics indirect resource utilization associated with symptomatic dengue infection.
Number of Dengue Infection Episodes - Clinical Symptom Since Onset of Suspected Dengue Cases: Temperature	From Day 0 to Year 3	Temperature, expressed in degrees Celsius (°C), was among symptoms of symptomatic dengue infection.
Number of Subjects With Laboratory Confirmed or Probable Dengue Cases According Symptomatic Dengue Definition (Primary, Secondary or Unknown) Among the Suspected Dengue Cases	From Year 0 to Year 3	A case of primary or secondary symptomatic dengue infection was defined as laboratory confirmed or probable symptomatic dengue case whose previous sample collected at scheduled Visits 1- 4 (Day 0- Year 3) to detect anti-dengue IgG antibodies was seronegative or seropositive, respectively. A probable dengue case was defined as a suspected symptomatic dengue case with the following laboratory findings: -anti-dengue IgM or anti-dengue IgG positivity in at least one sample (in either blood sample 1 or 2) AND no evidence of viremia (negative dengue virus identification through RT-qPCR) in blood sample 1 AND no evidence of anti-dengue Ig M or IgG seroconversion between blood sample 1 and blood sample 2.
Incidence of All Laboratory-confirmed or Probable Symptomatic Dengue Infection	At Year 3 (2014)	Incidence of laboratory confirmed or probable symptomatic dengue infection was assessed by calendar year and age strata. Note: In the study report the denominator for incidence estimation has not been expressed as an absolute number of subjects, but in person-years. Therefore, the category "number of subjects analysed" has been populated with the number of enrolled subjects attended the study visit after the specified season and in each age stratum.
Number of Primary Laboratory Confirmed Symptomatic Dengue Infection Cases	At Year 3 (2014)	Primary symptomatic dengue infection cases are defined as laboratory confirmed symptomatic dengue cases whose previous sample collected at scheduled visits to detect anti-dengue IgG antibodies were seronegative. Analysis was done by calendar year and age strata. Note: In the study report the denominator for incidence estimation has not been expressed as an absolute number of subjects, but in person-years. Therefore the category "number of subjects analysed" has been populated with the number of enrolled subjects seronegative for anti-dengue IgG antibodies before the specified season and attended the study visit after the specified season, and in each age stratum.
Number of Secondary Laboratory Confirmed Symptomatic Dengue Infection Cases	At Year 3 (2014)	Secondary symptomatic dengue infection cases are defined as laboratory confirmed symptomatic dengue cases whose previous sample collected at scheduled visits to detect anti-dengue IgG antibodies were seropositive. Note: In the study report the denominator for incidence estimation has not been expressed as an absolute number of subjects, but in person-years. Therefore the category "number of subjects analysed" has been populated with the number of enrolled subjects seropositive for anti-dengue IgG antibodies before the specified season and attended the study visit after the specified season, and in each age stratum.
Number of Laboratory Confirmed Dengue Infection Cases Associated With Caregiver Absenteeism	From 21 up to 35 days post laboratory confirmed dengue onset	The number of laboratory confirmed dengue infections with primary caregivers missing from work was recorded as part of health economics indirect resource utilization associated with symptomatic dengue infection.
Number of School Days Missed by Subjects	From 21 up to 35 days post laboratory confirmed dengue onset	The number of school days missed by subjects due to dengue infection were recorded as part of the dengue active surveillance and indirect resource utilization associated with symptomatic dengue infection.
Proportion of Subjects With Prevalence of Past Dengue Infection (Dengue Seroprevalence) at Enrollment	At Day 0 (At enrollment)	This outcome measures the occurrence of past dengue infections among subjects who had laboratory results. Proportion was estimated from logistic generalized estimating equations models (GEE) taking the clustering effect of the school into account and was presented per subject enrolment age. Immune response against dengue was assessed via Enzyme-linked Immunosorbent Assay (ELISA).
Proportion of Subjects With Primary Asymptomatic Dengue Infection	From Day 0 to Year 3	Asymptomatic dengue primary infection was defined as a documented seroconversion (anti-dengue IgG antibodies) between two sequential sera samples obtained during the scheduled visits, without suspicion of dengue. Proportion of asymptomatic dengue primary infection was analyzed among subjects who had no past dengue infection reported before the beginning of the period.
Number of Working Days Missed of Primary Care Giver 1 of Subjects With Laboratory Confirmed Symptomatic Dengue Cases	From 21 up to 35 days post laboratory confirmed dengue onset	The number of days off work from caregiver were recorded as part of health economics indirect resource utilization associated with symptomatic dengue infection.
Number of Laboratory Confirmed Dengue Infection Cases Associated With Subjects Absenteeism	From 21 up to 35 days post laboratory confirmed dengue onset	The number of laboratory confirmed dengue infection cases with subjects missing from school due to dengue infection were recorded as part of the dengue active surveillance and indirect resource utilization associated with symptomatic dengue infection.
Number of Subjects With Serious Adverse Events (SAEs)	From Day 0 to Year 3	Serious adverse events (SAEs) were collected on the enrolled subjects. SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject.
Number of Symptomatic Dengue Laboratory Confirmed Cases Associated With Hospitalization Direct Medical Resource	From Day 0 to Year 3	Direct medical resource included hospitalization, stay in intensive care units (ICU), medications, diagnostic and therapeutic procedures
Number of Hospitalization Days Due to Laboratory Confirmed Dengue Cases	From Day 0 to Year 3	Length of hospitalization was part of the direct medical resource, associated with dengue infection.
Number of Dengue Infection Episodes With Any Temperature Interval Since Onset of Suspected Dengue Cases, Among Laboratory Confirmed Dengue Cases	From Day 0 to Year 3	Temperature intervals assessed varied from hypothermia 33.5 to 36.4 degrees Celsius (°C), to normal temperature 36.5-35.9 °C and hyperthermia 37 - 39.9 °C, or were unknown.
Number of Laboratory Confirmed Dengue Episodes Associated With Clinical Symptoms	From Day 0 to Year 3	Dengue related clinical symptoms included general symptoms, digestive symptoms, respiratory symptoms, hemorrhagic symptoms and any other signs among first symptoms.