Epidemicity of cholera spread and the fate of infection control measures.

The fate of ongoing infectious disease outbreaks is predicted through reproduction numbers, defining the long-term establishment of the infection, and epidemicity indices, tackling the reactivity of the infectious pool to new contagions. Prognostic metrics of unfolding outbreaks are of particular importance when designing adaptive emergency interventions facing real-time assimilation of epidemiological evidence. Our aim here is twofold. First, we propose a novel form of the epidemicity index for the characterization of cholera epidemics in spatial models of disease spread. Second, we examine in hindsight the survey of infections, treatments and containment measures carried out for the now extinct 2010-2019 Haiti cholera outbreak, to suggest that magnitude and timing of non-pharmaceutical and vaccination interventions imply epidemiological responses recapped by the evolution of epidemicity indices. Achieving negative epidemicity greatly accelerates fading of infections and thus proves a worthwhile target of containment measures. We also show that, in our model, effective reproduction numbers and epidemicity indices are explicitly related. Therefore, providing an upper bound to the effective reproduction number (significantly lower than the unit threshold) warrants negative epidemicity and, in turn, a rapidly fading outbreak preventing coalescence of sparse local sub-threshold flare-ups.

On the predictive ability of mechanistic models for the Haitian cholera epidemic.

Predictive models of epidemic cholera need to resolve at suitable aggregation levels spatial data pertaining to local communities, epidemiological records, hydrologic drivers, waterways, patterns of human mobility and proxies of exposure rates. We address the above issue in a formal model comparison framework and provide a quantitative assessment of the explanatory and predictive abilities of various model settings with different spatial aggregation levels and coupling mechanisms. Reference is made to records of the recent Haiti cholera epidemics. Our intensive computations and objective model comparisons show that spatially explicit models accounting for spatial connections have better explanatory power than spatially disconnected ones for short-to-intermediate calibration windows, while parsimonious, spatially disconnected models perform better with long training sets. On average, spatially connected models show better predictive ability than disconnected ones. We suggest limits and validity of the various approaches and discuss the pathway towards the development of case-specific predictive tools in the context of emergency management.

Glucose- but not rice-based oral rehydration therapy enhances the production of virulence determinants in the human pathogen Vibrio cholerae.

Despite major attempts to prevent cholera transmission, millions of people worldwide still must address this devastating disease. Cholera research has so far mainly focused on the causative agent, the bacterium Vibrio cholerae, or on disease treatment, but rarely were results from both fields interconnected. Indeed, the treatment of this severe diarrheal disease is mostly accomplished by oral rehydration therapy (ORT), whereby water and electrolytes are replenished. Commonly distributed oral rehydration salts also contain glucose. Here, we analyzed the effects of glucose and alternative carbon sources on the production of virulence determinants in the causative agent of cholera, the bacterium Vibrio cholerae during in vitro experimentation. We demonstrate that virulence gene expression and the production of cholera toxin are enhanced in the presence of glucose or similarly transported sugars in a ToxR-, TcpP- and ToxT-dependent manner. The virulence genes were significantly less expressed if alternative non-PTS carbon sources, including rice-based starch, were utilized. Notably, even though glucose-based ORT is commonly used, field studies indicated that rice-based ORT performs better. We therefore used a spatially explicit epidemiological model to demonstrate that the better performing rice-based ORT could have a significant impact on epidemic progression based on the recent outbreak of cholera in Haiti. Our results strongly support a change of carbon source for the treatment of cholera, especially in epidemic settings.

Reassessment of the 2010-2011 Haiti cholera outbreak and rainfall-driven multiseason projections.

Mathematical models can provide key insights into the course of an ongoing epidemic, potentially aiding real-time emergency management in allocating health care resources and by anticipating the impact of alternative interventions. We study the ex post reliability of predictions of the 2010-2011 Haiti cholera outbreak from four independent modeling studies that appeared almost simultaneously during the unfolding epidemic. We consider the impact of different approaches to the modeling of spatial spread of Vibrio cholerae and mechanisms of cholera transmission, accounting for the dynamics of susceptible and infected individuals within different local human communities. To explain resurgences of the epidemic, we go on to include waning immunity and a mechanism explicitly accounting for rainfall as a driver of enhanced disease transmission. The formal comparative analysis is carried out via the Akaike information criterion (AIC) to measure the added information provided by each process modeled, discounting for the added parameters. A generalized model for Haitian epidemic cholera and the related uncertainty is thus proposed and applied to the year-long dataset of reported cases now available. The model allows us to draw predictions on longer-term epidemic cholera in Haiti from multiseason Monte Carlo runs, carried out up to January 2014 by using suitable rainfall fields forecasts. Lessons learned and open issues are discussed and placed in perspective. We conclude that, despite differences in methods that can be tested through model-guided field validation, mathematical modeling of large-scale outbreaks emerges as an essential component of future cholera epidemic control.