The Nicaraguan Pediatric Dengue Cohort Study: Incidence of Inapparent and Symptomatic Dengue Virus Infections, 2004–2010

<div><p>Dengue, caused by the four serotypes of dengue virus (DENV), is the most prevalent mosquito-borne viral disease of humans. To examine the incidence and transmission of dengue, the authors performed a prospective community-based cohort study in 5,545 children aged 2–14 years in Managua, Nicaragua, between 2004 and 2010. Children were provided with medical care through study physicians who systematically recorded medical consult data, and yearly blood samples were collected to evaluate DENV infection incidence. The incidence of dengue cases observed was 16.1 cases (range 3.4–43.5) per 1,000 person-years (95% CI: 14.5, 17.8), and a pattern of high dengue case incidence every other year was observed. The incidence of DENV infections was 90.2 infections (range 45.2–105.3) per 1,000 person-years (95% CI: 86.1, 94.5). The majority of DENV infections in young children (<6 years old) were primary (60%) and the majority of infections in older children (≥9 years of age) were secondary (82%), as expected. The incidence rate of second DENV infections (121.3 per 1,000 person-years; 95% CI: 102.7, 143.4) was significantly higher than the incidence rate of primary DENV infections (78.8 per 1,000 person-years; 95% CI: 73.2, 84.9). The rigorous analytic methodology used in this study, including incidence reporting in person-years, allows comparison across studies and across different infectious diseases. This study provides important information for understanding dengue epidemiology and informing dengue vaccine policy.</p></div

Incidence of DENV infections, Managua, Nicaragua, 2004–2010.

<p>The number of DENV infections from 2004–2005 to 2007–2008 has been previously reported <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002462#pntd.0002462-Balmaseda3" target="_blank">[16]</a>. The number of inapparent DENV infections in this paper vary slightly from our previous report due to the implementation of new quality control procedures which resulted in several revisions to the inapparent infection data.</p

Incidence of DENV infection outcomes by age.

<p>A. Dengue cases per 1,000 person-years at risk. B. DENV infections per 1,000 person-years at risk C. Dengue cases per 100 DENV infections.</p

Incidence of dengue cases among DENV infections, Managua, Nicaragua, 2004–2010.

<p>Incidence of dengue cases among DENV infections, Managua, Nicaragua, 2004–2010.</p

Incidence of primary and secondary DENV infections, Managua, Nicaragua, 2004–2010.

<p>The number of primary and secondary DENV infections from 2004–2005 to 2007–2008 has been previously reported <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002462#pntd.0002462-Balmaseda3" target="_blank">[16]</a>.</p

Flowchart of participants in the Pediatric Dengue Cohort Study, Managua, Nicaragua, 2004–2010.

<p>Flowchart of participants in the Pediatric Dengue Cohort Study, Managua, Nicaragua, 2004–2010.</p

Distribution of DENV serotypes in dengue cases by study year.

<p>The percent of dengue cases infected by each DENV serotype, of the total infections with known serotype, are shown. Three hundred and thirty-one (94%) of the 351 dengue cases had serotype information available. Two cases of co-infection were detected: one DENV-1 & DENV-4 co-infection in 2004–05 and one DENV-1 & DENV-2 co-infection in 2005–06. The distribution of DENV serotypes in dengue cases from 2004–2005 to 2007–2008 has been previously reported <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002462#pntd.0002462-Balmaseda3" target="_blank">[16]</a>.</p

Incidence of dengue cases in the cohort by study year and month, August, 2004–June, 2010.

<p>The number of dengue cases by month from 2004–2005 to 2007–2008 has been previously reported <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002462#pntd.0002462-Balmaseda3" target="_blank">[16]</a>.</p

Incidence of dengue cases, Managua, Nicaragua, 2004–2010.

<p>The number of dengue cases from 2004–2005 to 2007–2008 has been previously reported <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002462#pntd.0002462-Balmaseda3" target="_blank">[16]</a>.</p

Participant characteristics by year, Managua, Nicaragua, 2004–2010.

<p>The number of participants from 2004–2005 to 2007–2008 has been previously reported <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002462#pntd.0002462-Balmaseda3" target="_blank">[16]</a>.</p