Choléra

Résumé

Le choléra est une toxi-infection entérique épidémique contagieuse due à la bactérie Vibrio choleræ (« vibrion cholérique ») ou parfois aussi appelée « bacille virgule », découverte par l'anatomiste italien Filippo Pacini en 1854 et redécouverte par le bactériologiste allemand Robert Koch en 1884. Strictement limité à l'espèce humaine, le choléra se caractérise par des diarrhées brutales et très abondantes (gastro-entérite) menant à une sévère déshydratation. C’est une diarrhée infectieuse de type syndrome cholériforme ou diarrhée hydroélectrolytique (à diarrhée aqueuse) à ne pas confondre avec le syndrome gastro-entéritique (à diarrhée banale). La forme majeure classique peut causer la mort dans plus de la moitié des cas, en l’absence de thérapie par réhydratation orale (en quelques heures à trois jours). La contamination est orale, d’origine fécale, par la consommation de boissons ou d'aliments souillés. Cantonnées très longtemps à l'Asie (Inde, Chine et Indonésie), les épidémie

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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

Chargement

Competence-induced type VI secretion might foster intestinal colonization by Vibrio cholerae

Melanie Blokesch

The human pathogen Vibrio cholerae exhibits two distinct lifestyles: one in the aquatic environment where it often associates with chitinous surfaces and the other as the causative agent of the disease cholera. While much of the research on V. cholerae has focused on the host-pathogen interaction, knowledge about the environmental lifestyle of the pathogen remains limited. We recently showed that the polymer chitin, which is extremely abundant in aquatic environments, induces natural competence as a mode of horizontal gene transfer and that this competence regulon also includes the type VI secretion system (T6SS), a molecular killing device. Here, I discuss the putative consequences that chitin-induced T6SS activation could have on intestinal colonization and how the transmission route might influence disease outcome. Moreover, I propose that common infant animal models for cholera might not sufficiently take into account T6SS-mediated interbacterial warfare between V. cholerae and the intestinal microbiota.

Wiley-Blackwell2015

Chargement

Understanding the epidemiology of cholera, when and where it occurs and how it spreads, is key to its prevention and control. Models can help to apprehend cholera outbreaks by providing insight into critical epidemiological processes, and may be used to evaluate alternative intervention strategies or to predict the future course of epidemics. This thesis aims at advancing the evolution of spatially explicit epidemiological models of cholera outbreaks through methodological developments and practical applications. Over 160 years after John Snow first analyzed the spatial pattern of cholera cases in London and identified water as its pathway of contagion, the disease remains a major public health threat in many regions around the globe. It causes an estimated number of 2.86 (1.30 -- 4.00) million cases and 95 000 (21 000 -- 143 000) deaths in 69 endemic countries every year. A set of metapopulation and individual-based, mechanistic and semi-mechanistic epidemiological models has been developed to tackle epidemiological questions at the country, subnational and city scale. The models explicitly take into account the spatial variability of epidemiological processes such as the spread of the disease through hydrological connectivity and human mobility, or the high resolution spatiotemporal clustering of cases. A method to extract large-scale mobility fluxes from mobile phone call records and directly incorporate them into a model has also been established. Different environmental drivers of cholera epidemics have been taken into account. The models have been applied to recent cholera outbreaks in Haiti, Senegal, Chad and the Democratic Republic of the Congo. Results highlight the important part played by human mobility in the spreading of the disease and the influence of rainfall and other climatic variables as drivers of disease dynamics in several settings. applications demonstrate how models can inform epidemiological policy and show the effect of alternative intervention strategies on the course of an epidemic. The evaluation of the preventive allocation of oral cholera vaccine, antibiotics and/or water, sanitation and hygiene interventions within a given radius around reported cases in densely populated areas shows that such interventions are effective and efficient alternatives to mass intervention campaigns. Moreover, an alternative type of oral rehydration solution proves to have a significant effect on the course of a simulated epidemic. This thesis concludes that the explicit treatment of spatial heterogeneity at an appropriate scale is crucial to reproduce real-world dynamics of cholera outbreaks. It highlights how suitable models can address relevant questions about the dynamics of the disease, provide insights into ongoing epidemics, may aid emergency management and complement current epidemiological practice.

EPFL2017

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