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

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.

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.

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.

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).

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.

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 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.

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.

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.

Among virus types causing dengue infection were DENV-4 in 2012 and 2013 and DENV-1 in 2014, as assessed by PCR.

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.

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.

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.

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.

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.

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.

The number of days off work from caregiver were recorded as part of health economics indirect resource utilization associated with symptomatic dengue infection.

The number of days off work from caregiver were recorded as part of health economics indirect resource utilization associated with symptomatic dengue infection.

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.

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.

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.

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.

Direct medical resource included hospitalization, stay in intensive care units (ICU), medications, diagnostic and therapeutic procedures

Length of hospitalization was part of the direct medical resource, associated with dengue infection.

Temperature, expressed in degrees Celsius (°C), was among symptoms of symptomatic dengue infection.

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.

Dengue related clinical symptoms included general symptoms, digestive symptoms, respiratory symptoms, hemorrhagic symptoms and any other signs among first symptoms.