Cholera has been a public health burden in Ghana since the early 1970s. Between 1999 and 2005, a total of 25,636 cases and 620 deaths were officially reported to the WHO. In one of the worst affected urban cities, fecal contamination of surface water is extremely high, and the disease is reported to be prevalent among inhabitants living in close proximity to surface water bodies. Surface runoff from dump sites is a major source of fecal and bacterial contamination of rivers and streams in the study area. This study aims to determine (a) the impacts of surface water contamination on cholera infection and (b) detect and map arbitrary shaped clusters of cholera. A Geographic Information System (GIS) based spatial analysis is used to delineate potential reservoirs of the cholera vibrios; possibly contaminated by surface runoff from open space refuse dumps. Statistical modeling using OLS model reveals a significant negative association between (a) cholera prevalence and proximity to all the potential cholera reservoirs (R-2 = 0.18, p < 0.001) and (b) cholera prevalence and proximity to upstream potential cholera reservoirs (R-2 = 0.25, p < 0.001). The inclusion of spatial autoregressive coefficients in the OLS model reveals the dependency of the spatial distribution of cholera prevalence on the spatial neighbors of the communities. A flexible scan statistic identifies a most likely cluster with a higher relative risk (RR = 2.04, p < 0.01) compared with the cluster detected by circular scan statistic (RR = 1.60, p < 0.01). We conclude that surface water pollution through runoff from waste dump sites play a significant role in cholera infection. (C) 2010 Elsevier B.V. All rights reserved.