Calculatedwater system treatment requirements for entericpathogens based on achieving a health burden benchmark that accountsfor the likelihood and severity of illness were less than those basedon an annual probability of infection benchmark only when there wasevidence of a small likelihood of illness at low doses. Pathogen log(10) reduction targets for onsitenonpotablewater systems were calculated using both annual infection (LRTINF) and disability-adjusted life year (LRTDALY)benchmarks. The DALY is a measure of the health burden of a disease,accounting for both the severity and duration of illness. Resultswere evaluated to identify if treatment requirements change when accountingfor the likelihood, duration, and severity of illness in additionto the likelihood of infection. The benchmarks of 10(-4) infections per person per year (ppy) and 10(-6) DALYsppy were adopted along with multilevel dose-response modelsfor Norovirus and Campylobacter jejuni, which characterize the probability of illness given infection (Pill|inf)as dose-dependent using challenge or outbreak data. We found differencesbetween treatment requirements, LRTINF - LRTDALY, for some pathogens, driven by the likelihood of illness,rather than the severity of illness. For pathogens with dose-independentPill|inf characterizations, such as Cryptosporidium spp., Giardia, and Salmonella enterica, the difference, LRTINF - LRTDALY,was identical across reuse scenarios (<than 1.0). The differencesvaried across source waters and uses for C. jejuni and Norovirus and widened when the dose-dependentPill|inf was characterized using challenge data (i.e., when therewas evidence of a small probability of illness at low doses). Norovirus LRTs were highest across pathogens, despite lowseverity and dose-dependent Pill|inf, given the high infection riskspredicted by the multilevel framework. This work highlights updated Norovirus dose-response best practices, the quantitativeimpact of risk endpoint in determining risk-based treatment targets,and the discrepancy in best available science for illness and infectionresponses across pathogens.