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Translation of 1986 Criteria Risk to Equivalent Risk Levels for Use with New Health Data Developed Using Rapid Methods for Measuring Water Quality

Larry Wymer 1 , Tim Wade 2 and Al Dufour 1

1. National Exposure Research Laborato ry, 2. National Health and Environmental Effects Research Laboratory

In 1986, the Environmental Protection Agency published criteria for recreational waters (US EPA, 1986), based on epidemiological studies which related microbial water quality, as

measur ed by culture methods, to health effects in swimmers (Cabelli, 1983, Dufour, 1984). The
case definition for gastrointestinal (GI) illness was defined by symptoms or groups of symptoms. Highly credible gastrointestinal (HCGI) illness was defined by the fol lowing symptoms or symptom groups observed in the 8

- 10 days after the beach visit: (1) vomiting, (2) diarrhea with a fever or disabling enough for the individual to remain home, remain in bed or seek medical advice, or (3) stomachache or nausea accompanied by a fever. These combinations of symptoms were developed to strengthen the validity of using symptoms to describe gastrointestinal illness in swimmers, where the health status information was obtained by telephone interview.

In 2002 the EPA initiated the National Epidemiological and Environmental Assessment of Recreational (NEEAR) study program, a series of epidemiology studies to determine the relationship between health effects in swimmers and water quality that has been measured using
a new method that produces quantitative results in 2 to 3 hours (Wade et al ., 2008). By 2007, seven epidemiology studies had been completed, four at freshwater beaches and three at marine beaches. These studies used a more contemporary health case definition, “NEEAR GI ” (NGI), which differed from the HCGI symptoms used in the early EPA studies. Fever was no longer required to co

- occur with diarrhea, stomachache or nausea to meet a case definition of gastroenteritis, NGI still used multiple symptoms to describe gastroin testinal illness. NGI was defined as any of the following in the 10

- 12 days after the beach visit: (1) diarrhea (three or more loose stools in a 24 hour period); (2) vomiting; (3) nausea and stomachache; (4) nausea or stomachache, and interference with re gular activities (missed time from work or school, or missed other regular activities as a result of the illness).

One of the major differences between the early and recent studies is the broadening of the definition of an adverse health episode to includ e illnesses with gastrointestinal symptoms without fever as a pre

- requisite (with the exception of vomiting, which with or without fever is sufficient for an illness episode in both HCGI and NGI). This was done to capture episodes of gastroenteritis caused by viral infections ( e.g. , norovirus) which can often present with mild or no fever. Furthermore, this is consistent with definitions used in several recent longitudinal studies of gastroenteritis (Payment, 1991; Colford, 2002). International experts ha ve also suggested that a uniform international definition which does not require a fever and should include vomiting or diarrhea constituting greater than or equal to 3 soft stools in a 24 hour period (Majowicz, 2008). An additional difference was the exte nsion of the risk period for NGI by an average of approximately 2 days to 10

- 12 days. This was done to capture the longer incubation period for illnesses caused by some infectious organisms such as Cryptosporidium.2

The significant differences between the HCGI and NGI case definitions or health endpoints create a dilemma with regard to the risk level used to develop previous criteria for managing beach water quality. In the early EPA epidemiology studies (1986) the issue of risk level was resolved by using a simple algebraic equation that contained three known factors (1) the average density of the then current bacterial indicator, fecal coliforms, (2) the average density of the proposed indicator (enterococci or E. coli ) and (3) the standard density requi red for the beach water quality standard 200 fecal coliforms per 100 ml. Knowing these factors made it easy to calculate what the equivalent standard would be for the proposed indicator. This approach was used to develop the 1986 US EPA criteria (Dufour a nd Schaub, 2007). Based on these new standards and the health relationships that were derived for the proposed indicator, the implied attributable risk was 8 illnesses per 1000 swimmers in fresh water and 19 illnesses per 1000
swimmers in marine water.

T he question now is, how can one select a risk level using the new case definition for gastroenteritis that will be “as protective as” the currently used risk level under the old case definition? A logical approach to translating the currently used risk le vels based on the HCGI case definition (8 illnesses per 1000 swimmers for freshwater and 19 illnesses per 1000 swimmers for marine waters) to the NGI definition used in the NEEAR studies would be to equate a translation factor to the ratio of the non

- swimm er illness rates from the NEEAR study
relative to the non

- swimmer illness rates from the 1986 data, thus retaining a constant relative
risk. The non

- swimming illness rates of the two populations will give the best estimate of any inherent changes in the b ackground illness rates that may have occurred in the time between the 1986 and the 2009 studies, and provide an estimate of the effect of changing the case definition for gastroenteritis. Relative risk is the ratio of risk among an exposed population to that in an unexposed population (the baseline risk). The non

- swimmer illness rates represent the baseline. For relative risk to remain constant in the translation from HCGI to NGI, the respective swimmer illness rates must follow in proportion to the r espective baseline illness rates. Non

- swimmer
HCGI illness rates from the 1970

– 1980 US EPA epidemiology studies (Cabelli, 1983; Dufour, 1984) can be compared with the non

- swimmer NGI rates obtained from the NEEAR study data (Wade, 2008; Wade,2010). The n on

- swimmer HCGI illness rate from all of the early US EPA studies (Cabelli, 1983; Dufour, 1984) is 14 gastrointestinal illnesses per 1000 participants. The

non

- swimmer NGI illness rate from the NEEAR study data is 63 gastrointestinal illnesses per
1000 n on

- swimmer participants. (Wade, 2009; Wade, 2010) For a new criterion value to be “as protective as” the 1986 criteria, the relative risk of the two respective criterion values must be equal.

The acceptable risk limit of 8 illnesses per 1000 swimmers in freshwater refers to attributable risk, calculated by subtracting the illness rate in non

- swimmers from that in swimmers. The non

swimmer value must be added to the attributable risk value to obtain the total number of illnesses
in swimmers. The relative risk can be calculated by
RR = (attributable illness rate in swimmers + illness rate in non

- swimmers) /
illness rate in non

- swimmers Relative risk implied by the 1986 criteria for HCGI is RR = (8 + 14)/ 14 = 1.57 for freshwater3

In order to answer the question, what would an equivalent acceptable risk be for the same relative risk based on NGI in the NEEAR study, rearrange the above equation to obtain an Equivalent Risk Value (ERV) using a non

- swimmer NGI (NS NGI) rate of 63 per 1000 in place
of the NS HCGI rate of 14 per 1000. Using the freshwater relative risk as an example, this gives:
ERV = 1.57 (NS NGI rate)

– NS NGI rate = 1.57 (63)

- 63
= 36 Thus, an attributable risk of 36 NGI illnesses per 1000 swimmers represents an acceptable risk equivalent to 8 HCGI illnesses per 1000 swimmers.

The ERV for 19 GI illnesses per 1000 swimmers or any other suggested criterion value can be calculated the same way. First calculate a relative risk value for the acceptable risk and then use
the re lative risk value to calculate an ERV using the NGI value for non

- swimmers. A second, simpler way to calculate the ERV is to use the multiplication factor equal to the ratio of the NS
NGI illness rate to the NS HCGI illness rate. That value is 63/14= 4.5 . This is the translation factor for calculating the new risk level. Simply multiply the old criterion value by the translation factor to obtain an ERV that is “as protective as” the current criteria. For example, to
determine the ERV for 8 GI illnesses per 1000 swimmers, simply multiply 8 by 4.5 to obtain 36.

The translation factor of 4.5 represents the risk of NGI relative to HCGI and is key to this suggested approach to translating NGI risk in terms of HCGI. An approximate 95% confidence
interval f or this factor can be calculated to be 3.3 to 6.2. This assumes that non

- swimmer illness rates observed at the study areas (beaches) are representative of the variation in background illness among all coastal areas, and that this variation is described by a beta distribution (a common assumption when dealing in the variability of incidences which must fall in the range 0 to 100%).

Another question that must be addressed is, which risk level is to be translated, the freshwater
level or the marine water risk level? A direct comparison of the risk estimates for fresh and marine beach waters was carried out as described by Altman and Bland (2003) indicated that there were significant differences in the estimated risk levels only for limited range of

enteroco ccus CCE (approximately in the range of 100

- 126 CCE per 100 mL). Furthermore, a direct test of the slope parameters also shows that there is no difference in the slopes (p= 0.44), or the rate of increase in risk per unit increase in enterococci CCE, betwe en marine and freshwater beaches. A comparison based on the likelihood ratio test (as described by Wade, 2008), resulted in the same conclusion. For the likelihood ratio test the combined model was estimated with terms that allowed beach specific effects for the indicator term and the swimming term. However, this model was no better than a model with only a single term for each of these parameters (p = 0.19).

A likelihood ratio test was conducted the combined model was estimated with terms that allowed
b each specific effects for the indicator term and the swimming term. However, this model was no better than a model with only a single term for each of these parameters (p = 0.19).

In effect, there was little evidence for differences in risk estimates obta ined from separate models
from marine and freshwater beaches and the beach

- specific separate models showed no statistical4

improvement over a single combined model. On the basis of these, we present risk levels based on the combined model (Figure 1 ). Result s from the marine and freshwater studies indicate that

exposure

- response relationships are sufficiently similar to allow combining the newly

- developed freshwater and marine water data to give a single relationship between health effects and water quality m easured with a new rapid method. The relationship between swimming

- associated illness (SAI) per 1000 swimmers and water quality developed from the combined marine and freshwater data is defined by the equation:
SAI =

- 27.3 + 23.64(mean Log 10 qPCRCE)

which, for the purpose of calculating the qPCRCE (quantitative polymerase chain reaction cell equivalents) concentration for a new water quality criterion, is re

- arranged to:

mean Log 10 qPCRCE = (SAI + 27.3) / 23.64.

If the 8 illnesses per 1000 swimmers is translated into a NEEAR case definition level, the ERV is given by 36 illnesses per 1000 swimmers. Substituting the ERV of 36 for SAI in the equation above gives: mean Log 10 qPCRCE = (36 + 27.3 ) / 23.64 = 2.68

Antilog(2.6 8) = 471 = geometric mean(qPCRCE)

Thus, the risk level equivalent to 8 HCGI illnesses per 1000 swimmers is 36 NGI illnesses per 1000 swimmers and this relates to a geometric mean (GM) qPCRCE value of 471 per 100ml in
terms of the NEEAR case definition. An approach for translating the currently accepted risk levels for fresh and marine waters to equivalent risk levels appropriate for use with the new rapid qPCR method has been proposed in this document. The approach is appealing because:

- The approach is based on relative risk, which can be used with any case definition.

- The approach can be applied to any risk translation if a health, water quality relationship
is available.

- The approach is not dependent on what indicator or method is used to measure water quality.5

References

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Figure 1. Swimming

- Associated GI illness and Daily Average Enterococcus6

qPCR CCE

__ . All Subjects, marine and freshwater beaches combined (Intercept=

- 0.02730280, Slope= 0.02364574)