An Epidemiological Surveillance Study to Evaluate the Incidence of Dengue in Brazil

Incidence rate (IR) of laboratory-confirmed symptomatic dengue infection (lab-conf.) with 95% Confidence Interval (CI) for each year and overall, calculated as the incidence rate per 1000 person-years : numerator = number of all lab-conf. cases reported during the follow-up (FU) period at risk; denominator = total Person-years at risk, i.e. sum of FU periods at risk expressed in years until first Reverse Transcriptase quantitative Polymerase Chain Reaction (RT-qPCR) confirmed symptomatic dengue infection or subject's withdrawal, whichever came first. Lab-conf. case defined as follows: Dengue virus identification through RT-qPCR on acute serum sample or Dengue virus NS1 positive on acute serum sample through Enzyme-linked Immunosorbent Assay (ELISA) or Anti-Dengue Immunoglobulin type M (IgM) seroconversion between acute and convalescent serum samples through ELISA. Data were not analyzed by Dengue season as planned in the protocol as most of the cases occurred outside the seasons.

Time frame: At each calendar year i.e. Year 2014, 2015, 2016, 2017, 2018, and overall calendar years

Population: Analysis was performed on the According-to-Protocol cohort that included all evaluable subjects who met all eligibility criteria, complying with the procedures defined in the protocol and who had seroprevalence status at first visit of the first year.

Incidence rate (IR) of laboratory-confirmed or probable symptomatic dengue infection with 95% Confidence Interval (CI) by age category, and for each year separately and overall years calculated as the incidence rate per 1000 person-years : the numerator is the number of all laboratory-confirmed or probable symptomatic dengue infection cases reported during the follow-up period at risk; the denominator is the total Person-years at risk, i.e. sum of the follow-up periods at risk expressed in years. For early presenters, a probable case was that case without laboratory confirmation, presenting IgG positive in the convalescent sample; for late presenters, a probable case was the case without seroconversion of IgM, presenting at least one IgG positive in one sample (acute or convalescent). Data were not analyzed by Dengue season as planned in the protocol as most of the cases occurred outside the seasons.

Time frame: At each calendar year i.e. Year 2014, 2015, 2016, 2017, 2018, and overall calendar years

Population: Analysis was performed on the According-to-Protocol cohort that included all evaluable subjects who met all eligibility criteria, complying with the procedures defined in the protocol and who had seroprevalence status at first visit of the first year.

Incidence rate (IR) of laboratory-confirmed or probable symptomatic dengue infection with 95% Confidence Interval (CI) by gender, and for each year separately and overall years calculated as the incidence rate per 1000 person-years : the numerator is the number of all laboratory-confirmed or probable symptomatic dengue infection cases reported during the follow-up period at risk; the denominator is the total Person-years at risk, i.e. sum of the follow-up periods at risk expressed in years. For early presenters, a probable case was that case without laboratory confirmation, presenting IgG positive in the convalescent sample; for late presenters, a probable case was the case without seroconversion of IgM, presenting at least one IgG positive in one sample (acute or convalescent). Data were not analyzed by Dengue season as planned in the protocol as most of the cases occurred outside the seasons.

Time frame: At each calendar year i.e. Year 2014, 2015, 2016, 2017, 2018, and overall calendar years

Population: Analysis was performed on the According-to-Protocol cohort that included all evaluable subjects who met all eligibility criteria, complying with the procedures defined in the protocol and who had seroprevalence status at first visit of the first year.

Incidence rate (IR) of laboratory-confirmed or probable symptomatic dengue infection with 95% Confidence Interval (CI) by study site, and for each year separately and overall years calculated as the incidence rate per 1000 person-years : the numerator is the number of all laboratory-confirmed or probable symptomatic dengue infection cases reported during the follow-up period at risk; the denominator is the total Person-years at risk, i.e. sum of the follow-up periods at risk expressed in years. For early presenters, a probable case was that case without laboratory confirmation, presenting IgG positive in the convalescent sample; for late presenters, a probable case was the case without seroconversion of IgM, presenting at least one IgG positive in one sample (acute or convalescent). Data were not analyzed by Dengue season as planned in the protocol as most of the cases occurred outside the seasons.

Time frame: At each calendar year i.e. Year 2014, 2015, 2016, 2017, 2018, and overall calendar years

Population: Analysis was performed on the According-to-Protocol cohort that included all evaluable subjects who met all eligibility criteria, complying with the procedures defined in the protocol and who had seroprevalence status at first visit of the first year.

Incidence rate (IR) of virologically-confirmed symptomatic dengue infection with 95% Confidence Interval (CI) for each year separately and overall years calculated as the incidence rate per 1000 person-years : the numerator is the number of all virologically-confirmed dengue infection cases reported during the follow-up period at risk; the denominator is the total Person-years at risk, i.e. sum of the follow-up periods at risk expressed in years. A virologically confirmed symptomatic dengue infection is defined as a dengue case confirmed by RT-qPCR. Data were not analyzed by Dengue season as planned in the protocol as most of the cases occurred outside the seasons. Analysis was not performed by DENV-type as data would not be reliable due to the low number of cases reported.

Time frame: At each calendar year i.e. Year 2014, 2015, 2016, 2017, 2018, and overall calendar years

Population: Analysis was performed on the According-to-Protocol cohort that included all evaluable subjects who met all eligibility criteria, complying with the procedures defined in the protocol and who had seroprevalence status at first visit of the first year.

Incidence rate (IR) of primary inapparent dengue infection with 95% Confidence Interval (CI) by age category and, for each year separately and overall years calculated as the incidence rate per 1000 person-years, among subjects with no seroprevalence at the first visit: the numerator is the number of all primary inapparent dengue infection cases reported during the follow-up period at risk. The denominator is the total Person-years at risk, i.e. sum of the follow-up periods at risk expressed in years. The primary inapparent dengue infection condition was defined as a documented seroconversion (anti-dengue IgG antibodies) between two sequential sera samples obtained during the scheduled visits without clinical suspicion of dengue (identified during the time period in which seroconversion occurred). Data were not analyzed by Dengue season as planned in the protocol as most of the cases occurred outside the seasons.

Time frame: At each calendar year i.e. Year 2014, 2015, 2016, 2017, 2018, and overall calendar years

Population: Analysis was performed on the According-to-Protocol cohort that included all evaluable subjects who met all eligibility criteria, complying with the procedures defined in the protocol and who had no seroprevalence at first visit of the first year.

Incidence rate (IR) of primary inapparent dengue infection with 95% Confidence Interval (CI) by gender and, for each year separately and overall years calculated as the incidence rate per 1000 person-years, among subjects with no seroprevalence at the first visit: the numerator is the number of all primary inapparent dengue infection cases reported during the follow-up period at risk. The denominator is the total Person-years at risk, i.e. sum of the follow-up periods at risk expressed in years. The primary inapparent dengue infection condition was defined as a documented seroconversion (anti-dengue IgG antibodies) between two sequential sera samples obtained during the scheduled visits without clinical suspicion of dengue (identified during the time period in which seroconversion occurred). Data were not analyzed by Dengue season as planned in the protocol as most of the cases occurred outside the seasons.

Time frame: At each calendar year i.e. Year 2014, 2015, 2016, 2017, 2018, and overall calendar years

Population: Analysis was performed on the According-to-Protocol cohort that included all evaluable subjects who met all eligibility criteria, complying with the procedures defined in the protocol and who had no seroprevalence at first visit of the first year.

Incidence rate (IR) of primary inapparent dengue infection with 95% Confidence Interval (CI) by site and, for each year separately and overall years calculated as the incidence rate per 1000 person-years, among subjects with no seroprevalence at the first visit: the numerator is the number of all primary inapparent dengue infection cases reported during the follow-up period at risk. The denominator is the total Person-years at risk, i.e. sum of the follow-up periods at risk expressed in years. The primary inapparent dengue infection condition was defined as a documented seroconversion (anti-dengue IgG antibodies) between two sequential sera samples obtained during the scheduled visits without clinical suspicion of dengue (identified during the time period in which seroconversion occurred). Data were not analyzed by Dengue season as planned in the protocol as most of the cases occurred outside the seasons.

Time frame: At each calendar year i.e. Year 2014, 2015, 2016, 2017, 2018, and overall calendar years

Population: Analysis was performed on the According-to-Protocol cohort that included all evaluable subjects who met all eligibility criteria, complying with the procedures defined in the protocol and who had no seroprevalence at first visit of the first year.

A primary symptomatic dengue case is a subject with laboratory confirmed or probable symptomatic dengue infection, and without evidence of previous dengue infection (absence of Ig G antibodies at the previous scheduled visit and absence of laboratory confirmed symptomatic case detected previously at study surveillance). Analysis was not performed by DENV-type as data would not be reliable due to the low number of cases reported.

Time frame: From Year 2014 to Year 2018 (a range of 1 to 4 years for an individual subject)

Population: Analysis was performed on the laboratory confirmed or probable symptomatic dengue cases, excluding those reported without fever or reported before the first visit in the first year.

A secondary symptomatic dengue case is a subject with laboratory confirmed or probable symptomatic dengue infection, and with evidence of previous dengue infection (presence of IgG antibodies at the previous scheduled visit(s) or laboratory-confirmed symptomatic case detected previously at study surveillance). Analysis was not performed by DENV-type as data would not be reliable due to the low number of cases reported.

Time frame: From Year 2014 to Year 2018 (a range of 1 to 4 years for an individual subject)

Population: Analysis was performed on the laboratory confirmed or probable symptomatic dengue cases, excluding those reported without fever or reported before the first visit in the first year.

A subject was considered as having previous dengue infection at baseline, based on seroprevalence at first visit, namely if Dengue IgG positive (i.e. reactive) at first visit or if Laboratory-confirmed symptomatic dengue case detected at first visit (baseline).

Time frame: At the first visit of the first year

Population: Analysis was performed on the According-to-Protocol cohort that included all evaluable subjects who met all eligibility criteria, complying with the procedures defined in the protocol and who had seroprevalence status at first visit of the first year.

A subject was considered as having previous dengue infection at baseline, based on seroprevalence at first visit, namely if Dengue IgG positive (i.e. reactive) at first visit or if Laboratory-confirmed symptomatic dengue case detected at first visit (baseline).

Time frame: At the first visit of the first year

Population: Analysis was performed on the According-to-Protocol cohort that included all evaluable subjects who met all eligibility criteria, complying with the procedures defined in the protocol and who had seroprevalence status at first visit of the first year.

A subject was considered as having previous dengue infection at baseline, based on seroprevalence at first visit, namely if Dengue IgG positive (i.e. reactive) at first visit or if Laboratory-confirmed symptomatic dengue case detected at first visit (baseline).

Time frame: At the first visit of the first year

Population: Analysis was performed on the According-to-Protocol cohort that included all evaluable subjects who met all eligibility criteria, complying with the procedures defined in the protocol and who had seroprevalence status at first visit of the first year.

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

Time frame: From Year 2014 to Year 2018 (a range of 1 to 4 years for an individual subject)

Population: Analysis was performed on the Total cohort that included all subjects enrolled in the study.

To describe symptoms and spectrum of dengue disease in the study population for the suspected dengue cases, excluding those reported without fever. Suspected symptomatic dengue case= Febrile illness with body temperature ≥ 38°C measured (by any route) on at least two consecutive days and less than 14 days with or without the presence of other dengue symptoms or signs, without an obvious aetiology unrelated to dengue, based on investigator's judgement; Lab-confirmed = laboratory-confirmed symptomatic dengue cases; Probable = probable symptomatic dengue cases; Negative = negative symptomatic dengue cases; Indeterminate = indeterminate symptomatic dengue case( not classified as laboratory confirmed case, probable case or negative case); Severe dengue episode = at least one criteria met for severe dengue (in accordance to the dengue with warning signs and severe dengue definitions in the 2009 WHO guidelines for dengue).

Time frame: From Year 2014 to Year 2018 (a range of 1 to 4 years for an individual subject)

Population: Analysis was performed on the According-to-Protocol cohort that included all evaluable subjects who met all eligibility criteria, complying with the procedures defined in the protocol and who were defined as suspected dengue cases, excluding those without fever or reported before the first visit.