Trends in Patterns of Dengue Transmission over 4 Years in a Pediatric Cohort Study in Nicaragua

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 ~3,800 children initially aged 2-9 years old 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 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.

Serologic Imprint of Dengue Virus in Urban Haiti: Characterization of Humoral Immunity to Dengue in Infants and Young Children

“…24 Seroprevalence to any DENV serotype in two-year-old children olds varied from 22% to 40%, as determined by an enzyme-linked immunosorbent inhibition assay over a four-year period, in Nicaragua. 25 The high seroprevalence in Haiti would be consistent with the observation that DENV is a marker for the high degree of urban poverty and disruption of social services that characterized Port-au-Prince even before the recent earthquake. 26 The relative importance of dengue and malaria cannot be fully assessed from this study but the infrequent detection of malaria antibodies and the relative rarity of positive malaria smears at the GHESKIO clinic suggest malaria is not a dominant cause of febrile illness.…”

“…A model for assessing the impact of dengue has recently been implemented in Nicaragua in children more than two years of age. 28,29 Such careful prospective, denominator-based, clinical studies are necessary to determine the extent of severe clinical disease associated with acquisition of dengue in infants and young children in Haiti. Studies will need to be coupled with active case surveillance, molecular-based diagnosis, detailed study of the vector, risk factors in the environment, and serial serologic determinations.…”

Incidence of Dengue Virus Infection in School-Aged Children in Puerto Rico: A Prospective Seroepidemiologic Study

“…Our seroincidence rate was also comparable with the rates found in prospective cohort studies conducted in Central and South America (5.8-11.1%). 29,31,33 The similarity between our 1-year DENV seroincidence rates and other study populations suggests that Patillas and likely, Puerto Rico can also experience higher rates of DENV transmission.…”

“…[27][28][29]31 The reason for these differences is multifactorial and likely related to host population immune profile, DENV transmission patterns, DENV serotype/strain differences, and intensity of AFI monitoring. 34 For example, it seems that AFI detection methods used in studies may affect estimation of symptomatic-to-inapparent DENV infection ratios, because studies that used active AFI monitoring methods (e.g., school absence monitoring with student and parent follow-up) tended to report higher symptomaticto-inapparent DENV infection ratios (1:0.9-1:2.9) than studies using passive AFI monitoring methods (e.g., instructing participants to visit the study clinic when ill/no active followup; ratio = 1: 1.3-1:18).…”

“…34 For example, it seems that AFI detection methods used in studies may affect estimation of symptomatic-to-inapparent DENV infection ratios, because studies that used active AFI monitoring methods (e.g., school absence monitoring with student and parent follow-up) tended to report higher symptomaticto-inapparent DENV infection ratios (1:0.9-1:2.9) than studies using passive AFI monitoring methods (e.g., instructing participants to visit the study clinic when ill/no active followup; ratio = 1: 1.3-1:18). 25,27,28,31 This suggests that studies with more robust case detection methods are detecting more illness occurrences and produce more accurate symptomaticto-inapparent DENV infection ratio estimates. Although intrinsic DENV factors, host characteristics, and the interaction between pre-existing neutralization antibodies and the infecting DENVs may have influenced the inapparent DENV infection detected in our cohort, we believe that our study had comparable ratios of inapparent to symptomatic infections with those reported by others, because we used both active AFI methods (phone interviews) and passive methods (fever diary and EDSS + PDSS).…”