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Prediction of water-borne diseases is a critical aspect especially for developing countries. The current study focuses on cholera since it is considered to be a continuous public health threat. Vibrio cholerae, causative agent of cholera, is an autochthonous bacterial inhabitant in the aquatic environment and it is highly unlikely that cholera will ever be fully eradicated. Consequently, to reduce the disease burden, enhanced cholera prediction models that include several months' lead-time are still needed to further the development of effective mitigation and intervention strategies. Both regional- and large-scale environmental conditions can aid in understanding and predicting how and when outbreaks may occur. The overall goal of the research reported here was to develop a quantitative cholera prediction model with high quality, using regional and remote-sensing data from endemic and epidemic regions, respectively, in the Bengal Delta. This research involved four separate supporting objectives: 1) Determination of the role of environmental factors associated with the seasonality and modulating dynamics in a cholera outbreak; 2) Development of a physically plausible hypothesis of how local environmental factors modulate cholera outbreak dynamics; 3) Identification of the major environmental controls triggers sporadic cholera outbreaks in epidemic regions ; 4) Construction of an accurate model for the Bengal Delta simulating and predicting the two transmission routes of cholera (primary and secondary). The modeling results show that, for a high quality model > 70% Pseudo-R Square, Bengal Delta cholera in coastal regions is characterized by a single spring peak, whereas Bengal Delta cholera in inland regions occurs in bimodal peaks, with distinct hydroclimatological explanations for the geographical differences. Results confirm that spring season cholera is associated with coastal seawater intrusion, and fall cholera outbreaks are driven by floods related to the monsoon. This is the first study that demonstrates the relationship between in situ environmental conditions with regard to cholera outbreaks. Furthermore, results from remote-sensing data show that ambient temperature followed by high rainfall periods are the main triggers of cholera outbreaks in epidemic regions. These findings provide important steps and contributions toward development of environmental factor-based predictive models for cholera outbreaks in the Bengal Delta region.