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Background: Quantitative microbial risk assessment (QMRA) with Monte Carlo simulation is the process of estimating the risk of infection through exposure to microorganisms. Worldwide, certain Shiga-toxin-producing types of Escherichia coli, such as E coli O157:H7, have been recognised as pathogens leading to waterborne outbreaks of infection. We attempted to estimate the annual infection risk and the burden of disease posed by E coli O157:H7 in drinking water in the Gaza strip.Methods: In this prospective study, we applied the typical four steps of the QMRA technique: hazard identification, exposure assessment, dose-response analysis, and risk characterisation. Samples were collected between March, 2018, and January, 2019 from seven reference points in the drinking water supply from catchment to consumers' taps (water wells, small-scale water desalination plants, tanker trucks, desalinated water at households, municipal water at households, private wells, and private well water at households). Microbiological analysis was performed to identify E coli O157:H7 and log reduction values (LRVs) were calculated using probabilistic modelling for five catchment routes: water wells to household (LRV1), catchment well to desalination plant (LRV2), desalination plant to tanker truck (LRV3), tanker truck to household (LRV4), and private well to household (LRV5). The most probable number (MPN) table was used to obtain the MPN of E coli per 100 mL water sample. The probability of being infected through intake of E coli O157:H7 was estimated with a β-Poisson dose-response model. The estimated magnitude of health risk and burden of disease were determined using a stochastic modelling technique. Values were compared with the health-target-based risk values of the United States Environmental Protection Agency ([EPA] target ≤10-4 infection cases per-person per-year), and the WHO burden of disease values (target ≤10-6 disability adjusted life-years [DALYs] per-person per-year).Findings: Among 1317 water samples collected, E coli O157:H7 was detected in 91 (6·9%). The mean MPN was 1·97 (SD 9·74)/100 mL and the maximum was 112/100 mL. Negative LRVs were found in tanker trucks (LRV3 -1·465) and private household water wells (LRV5 -1·465), confirming water contamination. The risk model showed that the median of estimated annual risk of infection through consumption of water contaminated with E coli O157:H7 was 3·21 × 10-01 per-person per-year, which was about six logs higher than the EPA acceptable infection risk. The median disease burden was about 3·21 × 10-01 01 DALY per-person per-year, which greatly exceeded the WHO reference level.Interpretation: This study suggests the applicability and effectiveness of QMRA and highlights the necessity for a proactive strategy to incorporate a multibarrier approach to mitigate public health risks posed by contaminated drinking water.Funding: None. [ABSTRACT FROM AUTHOR]