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. 2010 Jan 1;201(1):5-14.
doi: 10.1086/648592.

Trends in patterns of dengue transmission over 4 years in a pediatric cohort study in Nicaragua

Angel Balmaseda  1 , Katherine Standish, Juan Carlos Mercado, Juan Carlos Matute, Yolanda Tellez, Saira Saborío, Samantha N Hammond, Andrea Nuñez, William Avilés, Matthew R Henn, Edward C Holmes, Aubree Gordon, Josefina Coloma, Guillermina Kuan, Eva Harris
Affiliations

Trends in patterns of dengue transmission over 4 years in a pediatric cohort study in Nicaragua

Angel Balmaseda et al. J Infect Dis. .

Abstract

Background: Dengue is the most prevalent mosquito-borne viral disease in humans and a major urban public health problem worldwide.

Methods: A prospective cohort study of approximately 3800 children initially aged 2-9 years was established in Managua, Nicaragua, in 2004 to study the natural history of dengue transmission in an urban pediatric population. Blood samples from healthy subjects were collected annually prior to the dengue season, and identification of dengue cases occurred via enhanced passive surveillance at the study health center.

Results: Over the first four years of the study, seroprevalence of anti-dengue virus (DENV) antibodies increased from 22%-40% in the 2-year-old cohort and 90%-95% in the 9-year-old cohort. The incidence of symptomatic dengue cases and the ratio of inapparent to symptomatic DENV infection varied substantially from year to year. The switch in dominant transmission from DENV-1 to DENV-2 was accompanied by an increase in disease severity but, paradoxically, a decrease in transmission. Phylogeographic analysis of full-length DENV-2 sequences revealed strong geographic clustering of dengue cases.

Conclusions: This large-scale cohort study of dengue in the Americas demonstrates year-to-year variation of dengue within a pediatric population, revealing expected patterns in transmission while highlighting the impact of interventions, climate, and viral evolution.

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Figures

Figure 1
Figure 1
A, Number of symptomatic dengue cases by month and year. B, Age-stratified incidence proportion of symptomatic dengue cases among subjects by age and year. C, Age-stratified incidence proportion of total DENV infection (symptomatic and inapparent) by year.
Figure 2
Figure 2
A, Proportion of symptomatic and inapparent DENV infections by year. B, Incidence proportion of symptomatic, inapparent and total DENV infections in 2007-8. Older children had a greater proportion of symptomatic infections compared to younger children. C, Percent of all DHF/DSS cases by year. 2006-7, DHF (n=1); 2007-8, DHF (n=5), DSS (n=3). The average age of DHF/DSS was 9.5 years-old. The average age of DHF/DSS cases was 9.5 years-old.
Figure 3
Figure 3
A, Percent primary and secondary immune response by age among symptomatic dengue cases. B. Percent primary and secondary immune response by age among all symptomatic and inapparent DENV infections. C, Percent primary and secondary cases by DENV serotype. DENV-2 was associated with a significantly higher percentage of secondary than primary cases as compared to DENV1; *, p<0.001.
Figure 4
Figure 4
A, Seroprevalence of anti-DENV antibodies by age cohort beginning with year of enrollment, showing the expected increase in anti-DENV antibodies over time. The 9-year old cohort has seroprevalence data through 2006, as subjects turning 12-years old were not re-enrolled in 2007 and therefore did not complete the 2007 annual sample. B, , Circulating DENV serotypes identified in symptomatic infections by year. There was 100% serotype concordance between RT-PCR and virus isolation for samples with positive results for both tests.
Fig. 5
Fig. 5
Geographic distribution of symptomatic cases by year and serotype.
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