BACKGROUND: Knowledge of spatial patterns of dengue virus (DENV) infection is 
important for understanding transmission dynamics and guiding effective disease 
prevention strategies. Because movement of infected humans and mosquito vectors 
plays a role in the spread and persistence of virus, spatial dimensions of 
transmission can range from small household foci to large community clusters. 
Current understanding is limited because past analyses emphasized clinically 
apparent illness and did not account for the potentially large proportion of 
inapparent infections. In this study we analyzed both clinically apparent and 
overall infections to determine the extent of clustering among human DENV 
infections.
METHODOLOGY/PRINCIPAL FINDINGS: We conducted spatial analyses at global and 
local scales, using acute case and seroconversion data from a prospective 
longitudinal cohort in Iquitos, Peru, from 1999-2003. Our study began during a 
period of interepidemic DENV-1 and DENV-2 transmission and transitioned to 
epidemic DENV-3 transmission. Infection status was determined by seroconversion 
based on plaque neutralization testing of sequential blood samples taken at 
approximately six-month intervals, with date of infection assigned as the 
middate between paired samples. Each year was divided into three distinct 
seasonal periods of DENV transmission. Spatial heterogeneity was detected in 
baseline seroprevalence for DENV-1 and DENV-2. Cumulative DENV-3 seroprevalence 
calculated by trimester from 2001-2003 was spatially similar to preexisting 
DENV-1 and DENV-2 seroprevalence. Global clustering (case-control Ripley's K 
statistic) appeared at radii of ∼200-800 m. Local analyses (Kuldorf spatial scan 
statistic) identified eight DENV-1 and 15 DENV-3 clusters from 1999-2003. The 
number of seroconversions per cluster ranged from 3-34 with radii from zero (a 
single household) to 750 m; 65% of clusters had radii >100 m. No clustering was 
detected among clinically apparent infections.
CONCLUSIONS/SIGNIFICANCE: Seroprevalence of previously circulating DENV 
serotypes can be a predictor of transmission risk for a different invading 
serotype and, thus, identify targets for strategically placed surveillance and 
intervention. Seroprevalence of a specific serotype is also important, but does 
not preclude other contributing factors, such as mosquito density, in 
determining where transmission of that virus will occur. Regardless of the 
epidemiological context or virus serotype, human movement appears to be an 
important factor in defining the spatial dimensions of DENV transmission and, 
thus, should be considered in the design and evaluation of surveillance and 
intervention strategies.