Detection of Vibrio cholerae O1 and O139 in environmental waters of rural Bangladesh: a flow-cytometry-based field trial

Presence of Vibrio cholerae serogroups O1 and O139 in the waters of the rural area of Matlab, Bangladesh, was investigated with quantitative measurements performed with a portable flow cytometer. The relevance of this work relates to the testing of a field-adapted measurement protocol that might prove useful for cholera epidemic surveillance and for validation of mathematical models. Water samples were collected from different water bodies that constitute the hydrological system of the region, a well-known endemic area for cholera. Water was retrieved from ponds, river waters, and irrigation canals during an inter-epidemic time period. Each sample was filtered and analysed with a flow cytometer for a fast determination of V. cholerae cells contained in those environments. More specifically, samples were treated with O1- and O139-specific antibodies, which allowed precise flow-cytometry-based concentration measurements. Both serogroups were present in the environmental waters with a consistent dominance of V. cholerae O1. These results extend earlier studies where V. cholerae O1 and O139 were mostly detected during times of cholera epidemics using standard culturing techniques. Furthermore, our results confirm that an important fraction of the ponds' host populations of V. cholerae are able to self-sustain even when cholera cases are scarce. Those contaminated ponds may constitute a natural reservoir for cholera endemicity in the Matlab region. Correlations of V. cholerae concentrations with environmental factors and the spatial distribution of V. cholerae populations are also discussed.

Rainfall mediations in the spreading of epidemic cholera

Enrico Bertuzzo, Marino Gatto, Lorenzo Mari, Lorenzo Righetto, Andrea Rinaldo

Following the empirical evidence of a clear correlation between rainfall events and cholera resurgence that was observed in particular during the recent outbreak in Haiti, a spatially explicit model of epidemic cholera is re-examined. Specifically, we test a multivariate Poisson rainfall generator, with parameters varying in space and time, as a driver of enhanced disease transmission. The relevance of the issue relates to the key insight that predictive mathematical models may provide into the course of an ongoing cholera epidemic aiding emergency management (say, in allocating life-saving supplies or health care staff) or in evaluating alternative management strategies. Our model consists of a set of dynamical equations (SIRB-like i.e. subdivided into the compartments of Susceptible, Infected and Recovered individuals, and including a balance of Bacterial concentrations in the water reservoir) describing a connected network of human communities where the infection results from the exposure to excess concentrations of pathogens in the water. These, in turn, are driven by rainfall washout of open-air defecation sites or cesspool overflows, hydrologic transport through waterways and by mobility of susceptible and infected individuals. We perform an a posteriori analysis (from the beginning of the epidemic in October 2010 until December 2011) to test the model reliability in predicting cholera cases and in testing control measures, involving vaccination and sanitation campaigns, for the ongoing epidemic. Even though predicting reliably the timing of the epidemic resurgence proves difficult due to rainfall inter-annual variability, we find that the model can reasonably quantify the total number of reported infection cases in the selected time-span. We then run a multi-seasonal prediction of the course of the epidemic until December 2015, to investigate conditions for further resurgences and endemicity of cholera in the region with a view to policies which may bring to the eradication of the disease in Haiti. The projections, although strongly depending on still uncertain epidemiological processes, show an endemic, seasonal pattern establishing in the region, which can be better forestalled by an improvement of the sanitation system only, rather than by vaccination alone. We thus conclude that hydrologic drivers and water resources management prove central to prediction, emergency management and long-term control of epidemic cholera. (C) 2013 Elsevier Ltd. All rights reserved.

Elsevier Sci Ltd2013

The role of aquatic reservoir fluctuations in long-term cholera patterns

Enrico Bertuzzo, Marino Gatto, Lorenzo Mari, Lorenzo Righetto, Andrea Rinaldo

We propose and analyze an important extension of standard cholera epidemiological models, explicitly accounting for fluctuations of water availability to the human community under study. The seasonality of water input in the reservoir drives the variation of concentration of Vibrio cholerae. Two compartments are added to the Susceptible-Infected-Bacteria model. First, the recovered individuals, which, over many seasons, lose their immunity to the disease and replenish the Susceptible group. Second, the water volume of the reservoir, which determines bacterial dilution and, consequently, the probability of contracting cholera by ingesting contaminated water. By forcing the model with a seasonally varying hydrologic input, we obtain simulations that can be compared to available data for various regions of the World characterized by different hydrological and epidemiological regimes. The model is shown to satisfactorily reproduce important characteristics of disease insurgence and long-term persistence. Using bifurcation analysis of nonlinear systems, we also explore how different degrees of seasonality and values of the basic reproductive number can change the expected long-term epidemiological time series. We find that there exist parametric conditions where the model shows chaotic patterns - i.e. high unpredictability especially in the amplitude of prevalence peaks - which very much resemble actual data on long-term cholera insurgence. (C) 2011 Elsevier B. V. All rights reserved.

2012

Hydrological, Anthropogenic and Ecological Processes in Cholera Dynamics

Lorenzo Righetto

The present Thesis deals with understanding, measuring and modelling epidemic cholera. The relevance of the endeavour stems from the fact that mathematical epidemiology, properly guided by model-guided field validation, is a reliable and powerful tool to monitor and predict ongoing epidemics in time for action, and to save lives through evaluation of the effectiveness of mitigation policies or the deployment of medical staff and supplies. In recent years, waterborne diseases – and cholera in particular – have consolidated their role as a major threat for developing countries, where sanitation conditions are poor and the vulnerability to extreme events is highest. Several important features controlling the dynamics of occurrence and spreading of the disease in a region are studied in the present Thesis, from both theoretical and experimental perspective. Understanding the basic processes that regulate cholera infection is key to build reliable prediction tools. In this Thesis several driving mechanisms of cholera are investigated, with the objective of connecting together hydro-climatology, ecology and epidemiology in a comprehensive framework. First, the role of water volume fluctuations is analyzed partly through a bifurcation study in a mostly theoretical assessment. Such work is then particularized in a field campaign carried out in rural Bangladesh, where hydro-climatological variables and Vibrio cholerae concentrations have been monitored for more than a year in one of the ponds constituting the local water reservoir. Concomitantly, a procedure for the detection of Vibrio cholerae, based on flow cytometry, is tested in the field. Further emphasis is also given to the role of human mobility in disseminating the disease among different communities. In particular, the contribution of human mobility in the dispersal of vibrios along the hydrologic network is specifically analyzed. All the knowledge collected in these studies is then used to add essential details to a modeling framework that is applied to the dramatic case of the Haiti epidemic. A spatially explicit model, taking into account both hydrological transport and human mobility, is developed to simulate the spreading of the disease since its onset. It is also shown that the resurgence of the disease, coinciding with the rainy season of June-July 2011, can only be reproduced if hydrological forcings are considered. The framework is tested by forcing it with synthetic rainfall scenarios and projecting epidemiological outputs. It is shown that the model can quantify correctly the number of cases in a given time span, even when calibrated with limited information. This result allows then to use it as a tool to assess a priori the effectiveness of intervention policies, such as vaccination and sanitation. The effect of these two is tested both in the short- and in the long-term, with different results. Such endeavour represents the ultimate goal of the work presented in this Thesis – albeit further effort is needed to link together public health management and mathematical epidemiology in this field.

EPFL2013

Rainfall mediations in the spreading of epidemic cholera

Enrico Bertuzzo, Marino Gatto, Lorenzo Mari, Lorenzo Righetto, Andrea Rinaldo

Elsevier Sci Ltd2013

Hydrological, Anthropogenic and Ecological Processes in Cholera Dynamics

Lorenzo Righetto

EPFL2013