Identifying determinants of heterogeneous transmission dynamics of the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea, 2015: a retrospective epidemiological analysis

Abstract

Objectives: To investigate the heterogeneous transmission patterns of Middle East respiratory syndrome (MERS) in the Republic of Korea, with a particular focus on epidemiological characteristics of superspreaders.

Design: Retrospective epidemiological analysis.

Setting: Multiple healthcare facilities of secondary and tertiary care centres in an urban setting.

Participants: A total of 185 laboratory-confirmed cases with partially known dates of illness onset and most likely sources of infection.

Primary and secondary outcome measures: Superspreaders were identified using the transmission tree. The reproduction number, that is, the average number of secondary cases produced by a single primary case, was estimated as a function of time and according to different types of hosts.

Results: A total of five superspreaders were identified. The reproduction number throughout the course of the outbreak was estimated at 1.0 due to reconstruction of the transmission tree, while the variance of secondary cases generated by a primary case was 52.1. All of the superspreaders involved in this outbreak appeared to have generated a substantial number of contacts in multiple healthcare facilities (association: p<0.01), generating on average 4.0 (0.0-8.6) and 28.6 (0.0-63.9) secondary cases among patients who visited multiple healthcare facilities and others. The time-dependent reproduction numbers declined substantially below the value of 1 on and after 13 June 2015.

Conclusions: Superspreaders who visited multiple facilities drove the epidemic by generating a disproportionate number of secondary cases. Our findings underscore the need to limit the contacts in healthcare settings. Contact tracing efforts could assist early laboratory testing and diagnosis of suspected cases.

Keywords: EPIDEMIOLOGY.

Figure 1

Epidemiological dynamics of the Middle East respiratory syndrome (MERS) in the Republic of Korea. (A) An epidemic curve of MERS in the Republic of Korea. The curve of daily cases is based on the date of illness onset. (B and C) Distributions of the number of secondary cases produced by each primary case. Using the percentile point, superspreaders were defined as cases that produced more than eight secondary cases. B was based on observed network data with 169 known links, while panel C rested on a partially reconstructed network with 182 links.

Figure 2

Transmission trees of the Middle East respiratory syndrome (MERS) in the Republic of Korea. The transmission trees describing who acquired infection from whom. Tree A was based on observed network data with 169 known links, while tree B rested on a partially reconstructed network with 182 links. Squares represent individual MERS cases, plotted according to their date of illness onset. Grey squares denote the superspreaders and the dotted squares are secondary cases caused by non-superspreaders. Each outer square represents the cluster of cases infected by a single super spreader at a particular healthcare facility. Cases without a known pathway of infection were grouped in the bottom within the dotted square. One unlinked case is known to have been infected by one of 13 cases in a single cluster in a hospital, but the corresponding case remains unlinked in this figure as it was not linked to any specific individual.

Figure 3

Cohort reproduction numbers of the Middle East respiratory syndrome (MERS) in the Republic of Korea, in 2015. Scatterplot of illness onset date and the number of secondary transmissions. The left panels distinguish cases into superspreaders and others, while the right panels show the distribution by visitors to multiple healthcare facilities and others. In each panel, the dashed grey line represents the value of unity below which the corresponding case does not contribute to the growth of the epidemic. A continuous line represents the time-dependent trend line.

Figure 4

Period reproduction numbers of the Middle East respiratory syndrome (MERS) in the Republic of Korea, in 2015. Estimated period reproduction number (R_t). The left panels distinguish cases into superspreaders and others, while the right panels show the distribution by visitors to multiple healthcare facilities and others. The observation period (from 11 May–29 June) is divided into three periods, and the reproduction number is assumed to be invariant in each period. The 95% CIs are indicated by dotted lines. A grey line shows the value of R_t=1.