These pathogens were chosen as ‘reference’ pathogens because (a) their DALY loss per case of disease was known, and (b) the dose-response data needed for QMRA were available for them. The 2006 WHO Guidelines showed that, for both restricted and unrestricted, irrigation the risk of rotavirus infection was higher than those of _Campylobacter_ and _Cryptosporidium_ infection, and thus rotavirus infection risks could be used on their own to assess the safety of wastewater-irrigation practices.

However, dose-response data for norovirus (formerly called Norwalk virus or Norwalk-like virus) are now available (Teunis _et al_ ., 2008). Norovirus is a better reference viral pathogen than rotavirus as it has a very high infectivity and causes diarrheal disease in both adults and children (whereas rotavirus causes diarrhea mainly in very young children). Thus norovirus is now considered the reference viral pathogen of choice for wastewater-use QMRA.

As shown in section A.3 of Annex A, the tolerable maximum norovirus infection risk, corresponding to a tolerable maximum additional burden of disease of 10<sup>−4</sup> DALY loss pppy, is 0.14 pppy, which means that an individual will become infected with norovirus once every seven years.

_Step 3: Conduct QMRA-MC risk simulations to determine required minimum total norovirus reductions for both restricted and unrestricted irrigation_ The current state-of-the-art for conducting QMRA risk simulations comprises:

1. Use of norovirus as the reference viral pathogen.

2. Use of an improved method for calculating annual infection risks by QMRA-MC (Karavarsamis and Hamilton, 2010), which is explained in section A.2 of Annex A.

3. Exposure scenarios:

- _Unrestricted irrigation:_ consumption of wastewater-irrigated salad crops (typically lettuce as a non-root crop and onions as a root crop).

- _Restricted irrigation:_ involuntary ingestion of wastewater-saturated soil particles. This is a likely scenario as wastewater-saturated soil would contaminate the fieldworkers’ fingers and some pathogens could be transmitted to their mouths and hence ingested. Two sub-scenarios are used: labor-intensive agriculture (typical of low-income countries) and highly mechanized agriculture (middle- and high-income countries).

4. Selection of a locally appropriate range of values for each parameter in the QMRA risk simulation—see Table A.7 of Annex A.

5. The QMRA-MC norovirus program for restricted irrigation is now run with the locally appropriate parameter ranges,<sup>19</sup> and then the QMRA-MC norovirus program for unrestricted irrigation is run.<sup>20</sup> The QMRA-MC results show the required log unit norovirus reductions which ensure that the tolerable maximum norovirus infection risk of 0.14 pppy is not exceeded.<sup>21</sup> 19 See the Note at the end of Annex A concerning the availability of these QMRA-MC computer programs.

20 See Mara and Sleigh (2010d) for practical details on running QMRA-MC programs. Tables A.5, A.6 and A.9 in Annex A show typical simulated norovirus infection risks.

21 Log unit reductions are log10 unit reductions. Thus a 1-log unit reduction = a 90% reduction, a 2-log unit reduction = a 99% reduction, a 3-log unit reduction = a reduction of 99.9%, and so on.

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