Spatial dimensions of dengue virus transmission across interepidemic and epidemic periods in Iquitos, Peru (1999-2003)

Abstract

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.

Figure 1. Distribution of cohort participant houses throughout the 8 zones of Iquitos.

Each circle marks the location of a participant home.

Figure 2. Distribution of all participants sampled during 4-month interval.

Black = DENV-3 susceptible, red = DENV-3 infected, green = DENV-3 immune.

Figure 3. Seroprevalence of DEN-1 and DEN-2 in the 8 geographic zones of Iquitos in October 1999.

Clusters of DENV-1 are indicated by colored circles (purple = May–Aug 1999; red = Jan–Apr 2000; pink = Sep–Dec 2001; green = Jan–Apr 2002). No significant clusters of DENV-2 were identified during the study period.

Figure 4. Seroprevalence of DEN-3 by trimester.

Pink circles indicate significant clusters.

Figure 5. Seroprevalence kernel of DENV-3 by trimester.

Figure 6. Monte Carlo K statistic.

The difference between the observed and expected over the expected is plotted against distance, r. The grey envelope is the 99% probability envelope based on the pattern of controls and the black line is the K function ofor the cases (seroconversions). If the line strays above the envelope, this indicates clustering. If it strays below, this indicates repulsion or over dispersion.