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. 2016 Feb 4;10(2):e0004337.
doi: 10.1371/journal.pntd.0004337. eCollection 2016 Feb.

Incidence of Dengue Virus Infection in Adults and Children in a Prospective Longitudinal Cohort in the Philippines

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Incidence of Dengue Virus Infection in Adults and Children in a Prospective Longitudinal Cohort in the Philippines

Maria Theresa Alera et al. PLoS Negl Trop Dis. .

Abstract

Background: The mean age of dengue has been increasing in some but not all countries. We sought to determine the incidence of dengue virus (DENV) infection in adults and children in a prospective cohort study in the Philippines where dengue is hyperendemic.

Methodology/principal findings: A prospective cohort of subjects ≥6 months old in Cebu City, Philippines, underwent active community-based surveillance for acute febrile illnesses by weekly contact. Fever history within the prior seven days was evaluated with an acute illness visit followed by 2, 5, and 8-day, and 3-week convalescent visits. Blood was collected at the acute and 3-week visits. Scheduled visits took place at enrolment and 12 months that included blood collections. Acute samples were tested by DENV PCR and acute/convalescent samples by DENV IgM/IgG ELISA to identify symptomatic infections. Enrolment and 12-month samples were tested by DENV hemagglutination inhibition (HAI) assay to identify subclinical infections. Of 1,008 enrolled subjects, 854 completed all study activities at 12 months per-protocol undergoing 868 person-years of surveillance. The incidence of symptomatic and subclinical infections was 1.62 and 7.03 per 100 person-years, respectively. However, in subjects >15 years old, only one symptomatic infection occurred whereas 27 subclinical infections were identified. DENV HAI seroprevalence increased sharply with age with baseline multitypic HAIs associated with fewer symptomatic infections. Using a catalytic model, the historical infection rate among dengue naïve individuals was estimated to be high at 11-22%/year.

Conclusions/significance: In this hyperendemic area with high seroprevalence of multitypic DENV HAIs in adults, symptomatic dengue rarely occurred in individuals older than 15 years. Our findings demonstrate that dengue is primarily a pediatric disease in areas with high force of infection. However, the average age of dengue could increase if force of infection decreases over time, as is occurring in some hyperendemic countries such as Thailand.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Study flow chart.
Fig 2
Fig 2. Dengue virus (DENV) hemagglutination inhibition (HAI) profiles at enrolment in different age groups.
Fig 3
Fig 3. Proportion of symptomatic dengue virus (DENV) infections among all per-protocol subjects with different DENV hemagglutination inhibition (HAI) profiles at enrolment.
Negative HAI: 4/125; monotypic HAI: 2/19; multitypic HAI: 7/710 (chi-square, p<0.001). Three symptomatic cases in non-per-protocol subjects were not included because HAI testing was not completed.
Fig 4
Fig 4. Proportion of symptomatic dengue virus (DENV) infections among total (symptomatic and subclinical) DENV infections in per-protocol subjects with different DENV hemagglutination inhibition (HAI) profiles at enrolment.
Negative HAI: 4/12; monotypic HAI: 2/5; multitypic HAI: 7/57 (chi-square, p = 0.068). Three symptomatic cases were not included because of missing HAI titers.
Fig 5
Fig 5. Proportion of subjects of different ages that were dengue seropositive at enrolment (shown in black).
Fit of model 1 assumed constant force of infection (shown in blue). Fit of model 2 assumed non-constant force of infection (shown in red).
Fig 6
Fig 6. Proportion of dengue naïve subjects at enrolment that seroconverted at 12 months.

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