Background:
Planning interventions to respond to cholera epidemics requires an understanding of the major transmission routes. Interrupting short-cycle (household, foodborne) transmission may require different approaches as compared long-cycle (environmentally-mediated/waterborne) transmission. However, differentiating the relative contribution of short- and long-cycle routes has remained difficult, and most cholera outbreak control efforts focus on interrupting long-cycle transmission. Here we use high-resolution epidemiological and municipal infrastructure data from a cholera outbreak in 1853 Copenhagen to explore the relative contribution of short- and long-cycle transmission routes during a major urban epidemic.

Methodology/Principal findings:
We fit a spatially explicit time-series meta-population model to 6,552 physician-reported cholera cases from Copenhagen in 1853. We estimated the contribution of long-cycle waterborne transmission between neighborhoods using historical municipal water infrastructure data, fitting the force of infection from hydraulic flow, then comparing model performance. We found the epidemic was characterized by considerable transmission heterogeneity. Some neighborhoods acted as localized transmission hotspots, while other neighborhoods were less affected or important in driving the epidemic. We found little evidence to support long-cycle transmission between hydrologically-connected neighborhoods. Collectively, these findings suggest short-cycle transmission was significant.

Conclusions/Significance:
Spatially targeted cholera interventions, such as reactive vaccination or sanitation/hygiene campaigns in hotspot neighborhoods, would likely have been more effective in this epidemic than control measures aimed at interrupting long-cycle transmission, such as improving municipal water quality. We recommend public health planners consider programs aimed at interrupting short-cycle transmission as essential tools in the cholera control arsenal.

Author summary:
John Snow’s seminal work on the London cholera epidemic and Broadway pump helped establish cholera as a quintessential waterborne (long-cycle) pathogen. However, there is renewed interest in the role that short-cycle (e.g. food-borne and household) transmission plays in epidemic contexts. The distinction between transmission pathways can be important, as they may demand different interventions. However, disentangling these pathways requires high-quality epidemiological and contextual data that is rarely collected in outbreak situations. Here we use detailed cholera incidence and municipal infrastructure data from a cholera outbreak in 1853 Copenhagen to estimate the relative contributions of short- and long-cycle transmission to the epidemic. We find transmission between neighborhoods during the epidemic did not follow water pipe connections, suggesting little evidence of long-cycle transmission. Instead, we suggest that short-cycle transmission was likely critical to the propagation of the outbreak. Interventions targeting short-cycle transmission are important tools that merit further consideration by public health officials combating epidemic cholera.