Space-time analysis of hospitalised dengue patients in rural Thailand reveals important temporal intervals in the pattern of dengue virus transmission

Abstract

Objective: To determine the temporal intervals at which spatial clustering of dengue hospitalisations occurs.

Methods: Space-time analysis of 262 people hospitalised and serologically confirmed with dengue virus infections in Kamphaeng Phet, Thailand was performed. The cases were observed between 1 January 2009 and 6 May 2011. Spatial coordinates of each patient's home were captured using the Global Positioning System. A novel method based on the Knox test was used to determine the temporal intervals between cases at which spatial clustering occurred. These intervals are indicative of the length of time between successive illnesses in the chain of dengue virus transmission.

Results: The strongest spatial clustering occurred at the 15-17-day interval. There was also significant spatial clustering over short intervals (2-5 days). The highest excess risk was observed within 200 m of a previous hospitalised case and significantly elevated risk persisted within this distance for 32-34 days.

Conclusions: Fifteen to seventeen days are the most likely serial interval between successive dengue illnesses. This novel method relies only on passively detected, hospitalised case data with household locations and provides a useful tool for understanding region-specific and outbreak-specific dengue virus transmission dynamics.

Figure 1

The DENV transmission cycle. Human hosts are represented by timelines A, B₁, and B₂. The vector is represented by timeline V. The cycle begins when susceptible host A acquires an infection from a vector (not shown) at the upper left. The vector, V, takes a blood meal from host A during the infectious period. After the extrinsic incubation period, the cycle is completed when DENV is transmitted to susceptible hosts B₁ and B₂. The serial interval between successive illnesses is depicted with the thick gray arrows.

Figure 2

The study site and household locations of DENV-infected, hospitalized individuals. The black line is the boundary of the Mueang District of Kamphaeng Phet, Thailand. The gray shaded area is the Nai Mueang Subdistrict, and the Ping River is depicted in light blue.

Figure 3

The times series plot for hospitalized dengue patients included in this research. The asterisk denotes that the count for April 2011 includes 5 cases with onset of illness between May 1, 2011 and May 3, 2011.

Figure 4

Space-time clustering results. The bars indicate the number of hospitalized dengue patients with the same infecting serotype that resided within the stated distance of each other. The results are shown for distances of 100m, 200m, 300m, 400m, and 500m. The black dashed line indicates the expected number of cases under the null hypothesis of no space-time interaction. The dashed red line indicates the 99.98^th percentile of the permutation distribution. Bars exceeding this line have a nominal significance level less than 0.0002, and a Bonferroni adjusted significance level less than 0.05.

Figure 5

The excess risk of dengue patient hospitalization due to the space-time interaction between cases. Spatial and temporal distances are from a previous hospitalized case.