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Indicators for Waterborne Pathogens (2004)

Chapter: 2 Health Effects Assessment

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Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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2
Health Effects Assessment

INTRODUCTION

The foremost goal of developing and using indicators for waterborne pathogens is public health protection. This chapter provides an overview of health effects assessment for waterborne pathogens and their indicators, and includes a brief review of surveillance and epidemiologic study designs, an historical review and current status of health effects assessment, and a detailed discussion of quantitative microbial risk assessment. Furthermore, health effects assessment is discussed throughout this chapter in the context of drinking water and of fresh and marine recreational waters. This chapter also includes a description of the national surveillance system for waterborne disease outbreaks and several related epidemiologic studies currently being conducted. The final section is a summary of the chapter and its conclusions and recommendations.

This chapter is not intended to serve as a comprehensive review of epidemiology as a methodologic tool or waterborne disease in humans, both of which are beyond the scope of this report. Rather, it provides some substantive background information on epidemiology and health effects assessment within the overall context of indicators for waterborne pathogens as discussed throughout this report and especially in support of a phased approach to microbial water quality monitoring that is provided in Chapter 6.

Approaches to Health Effects Assessments

Health effects assessments for waterborne pathogens can be based on a number of approaches, all of which have been used to document and quantify the

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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health risks resulting from microorganisms in water. These approaches include (1) assessments of epidemiologic evidence for waterborne-based outbreaks; (2) human volunteer studies showing that a known or potential waterborne pathogen is infectious by the oral ingestion route and capable of causing infection and disease at particular doses (dose-response studies); (3) various types of retrospective and prospective epidemiologic studies for health effects assessments; (4) estimates of health risks by linking epidemiologic evidence for disease to measured concentrations of either pathogens or indicators in the water; (5) estimates of the ratios of pathogens to indicators in the exposure vehicle (e.g., feces, sewage, fecally contaminated water); and (6) quantitative microbial risk assessments that integrate human exposure and health effects data for quantitative risk estimations or characterizations.

Health Effects Concerns and Early Studies of Microbial Water Quality

Outbreak Investigations and Risk Estimates from Pathogen-to-Indicator Ratios in Water

As discussed in Chapter 1, concerns about the sanitary quality of drinking water and the risks of enteric infectious diseases in the United States go back to at least the late 1800s, when enteric disease outbreaks were first recognized and linked at least tentatively to these exposure routes. Similar concerns for U.S. recreational and shellfish waters started in the 1920s. The initial recognition of and concern about infectious disease risks from these sources of exposure focused on enteric bacterial diseases, and early health effects assessments of enteric bacterial pathogens and waterborne outbreaks date back to the early 1920s. Human health risks from enteric viruses and parasites in water were first recognized and addressed during and shortly after World War II. However, civilian risks from these waterborne pathogens were not widely documented and appreciated until studies of waterborne outbreaks and waterborne pathogen occurrence were first reported in the 1960s. The recognized viral and protozoan pathogens of initial concern were infectious hepatitis viruses, polio, and other enteroviruses, and Entamoeba histolytica and Giardia lamblia, respectively.

Perhaps the first attempts at linking health effects assessments of waterborne pathogens to microbial water quality were based on ratios of Salmonella typhi to fecal indicator (coliform) bacteria in feces and sewage and the allowable limits of coliforms in drinking water and, later, in recreational bathing and shellfish waters (Kehr and Butterfield, 1943; Prescott et al., 1945).

Early Health Effects Assessments of Enteric Pathogens from Human Dose-Response Studies

The first human health effects dose-response studies appear to be with the

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
×

protozoan parasites Entamoeba histolytica and other Entamoeba species conducted using enemy prisoners in the Philippines by U.S. Army medical officers early in the twentieth century (Walker and Sellards, 1913). This study also showed for the first time that E. histolytica caused dysentery, that the cysts and trophozoites (see also Chapter 3) were different forms of the same microorganism, and that other Entamoeba species (notably Entamoeba coli) did not cause dysentery or other enteric disease. It was not until the 1950s that a researcher attempted to determine the number of enteric parasites necessary to cause infection in human dose-response studies with Entamoeba coli (Rentdorff, 1954a) and Giardia lamblia (Rentdorff, 1954b). Dose-response data on bacterial infectivity from human volunteer studies date back to at least the 1940s when different doses of Shigella paradysenteriae (now S. flexneri) were administered in vaccine trials (Shaughnessy et al., 1946).

For enteric viruses, the first human volunteer studies were with infectious hepatitis viruses during and after World War II (Cameron, 1943; Lainer, 1940; MacCallum and Bradley, 1944; Voegt, 1940). Studies by MacCallum and Bradley’s group are considered the first to distinguish infectious from serum hepatitis. Some of these early studies provided the first dose-response data for infectious hepatitis, but lack of knowledge about actual virus concentrations in the inocula has hampered the use of these data and subsequent infectious hepatitis human volunteer dose-response data for health risk assessments. Studies to estimate dose-response for virus infectivity were conducted using candidate live oral poliovirus vaccines in the 1950s (Koprowski, 1956; Sabin, 1955) and 1960s (Katz and Plotkin, 1967), and infectivity for humans could be related to virus concentrations as measured by other methods. Mathematical modeling of the data sets, taking into account the number of subjects used at each dose and the sensitivity of the dose-response study, was not undertaken until the 1980s (Haas, 1983b). However, many data sets, along with the best-fit models for bacteria, protozoa, and viruses, have since been compiled (Haas et al., 1999b).

Prospective Epidemiologic Studies of Microbial Water Quality and Health Effects

Prospective epidemiologic studies have attempted to link health effects in exposed individuals to the microbial quality of water. This approach has been used primarily for recreational waters and dates back to studies by Stevenson (1953) on Lake Michigan and the Ohio River. Those studies reported epidemiologically detectable health effects in bathers from waters containing about 2,300-2,400 total coliforms per 100 mL. Based on several lines of evidence—including outbreak data, the ratios of Salmonella typhi to fecal indicator (coliform) bacteria in feces and sewage, and epidemiologic studies of enteric illness in bathers at beaches having different levels of fecal contamination—the U.S. Public Health Service (USPHS) and later the Federal Water Pollution Control Association

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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(FWPCA; predecessor to the U.S. Environmental Protection Agency) developed bacteriological quality guidelines for recreational waters, as noted in Chapter 1 (Cox, 1951; NTAC, 1968; Scott, 1951).

Public Health Risk Assessment Framework

The ultimate objective of determining the microbiological quality of water is to identify and then minimize the public health risk from consuming water intended for drinking and from exposure to recreational water. Data are used to develop approaches to remediate or control this public health risk by reducing the potential exposure to levels that are considered acceptable (e.g., by controlling contamination sources) or developing communication strategies to prevent exposure (e.g., by closing a beach).

Indicators are measured for many purposes (see Chapter 4 for a detailed discussion of indicator applications). In terms of public health protection, indicators for pathogens in water intended for drinking are measured to determine the level of microbial contamination of source water (see also Chapter 6), whether existing water treatment processes are adequate, and whether the integrity of the distribution system has been breached. In addition, indicators can be used to measure the quality of the water in unregulated private wells. The measurement of indicators in the recreational water setting is typically conducted to determine if the level of contamination of surface waters such as oceans, lakes, and rivers is sufficiently elevated to pose a human risk and, therefore, to determine whether warnings should be issued or recreational waters should be closed to the public.

In drinking water and food, philosophically a zero-tolerance approach has been taken for indicators. Thus, it is presumed that if a measured indicator concentration is zero through water protection and treatment, the health risk is also zero. However, this traditional strategy does not provide an effective framework for decision making in the context of what is currently known about indicators. All ambient waters (including groundwater) will be subject to some level of microbial indicators and contamination whether associated with fecal sources (both human and nonhuman) or with naturally occurring microorganisms. Thus, the regulatory question remains, What measurable microorganisms in water best represent a risk to human health and at what levels would they be of concern?

Such criteria and standards can be established by determining two relationships: (1) between the density of the indicators and the occurrence of adverse health outcomes, and (2) between the density of the indicators and the presence of pathogenic organisms in the water. Although the association between the occurrence of a pathogen (or its indicator) in water and a human health effect is a difficult one to determine, epidemiologic studies, surveillance, and risk assessment are useful tools to help establish this association.

Risk assessment is a process that allows for the integration of scientific data

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
×

regarding an environmental hazard into a framework that addresses the risk of exposure and its potential health impacts (NRC, 1983). The process is quantitative in nature and attempts to address both the nature and the magnitude of the risk. This process has proven invaluable to the regulatory community, industry, and risk managers and has direct application to public health risk from water. The value of such a framework is that many different types of information—various indicator data, epidemiologic data, and data specific to the nature of the exposure (e.g., recreational or irrigation waters versus source of potable water supply)—can be used to define public health safety goals.

In ambient recreational waters, there is a need to understand the nature and level of the risk and, therefore, to take a risk assessment approach. In the risk assessment process, hazard identification has traditionally been separated from exposure analysis. In this case, the nature of the microbial hazard and its identification are closely tied to the sources and fate of the pathogenic microorganisms and, thus, the exposure. For example, enteric viruses detected at beaches can be tied to human fecal inputs and the ability of the virus to survive and cause illness at low doses and concentrations.

Many attributes of indicators (see Chapter 4 for further information) and indicator methods that may lend themselves to the risk assessment process are currently available (e.g., identifying sources of microbial contamination), whereas other attributes will be difficult to determine and may not prove feasible (e.g., establishing a quantitative relationship between concentrations of indicators and the degree of public health risk). As in most science-based evaluations, uncertainty will have to be described, and quantifying uncertainty is most problematic in the exposure portion of the analysis where indicators are used to estimate the potential for exposure to actual pathogens. A microbial risk framework can be developed and used to understand the basic principles and data gaps in the study of public health risks associated with the characterization of recreational water quality using a variety of methodologies. Such an approach will lead to a decision support system for data gathering (types of data and methods) and for response and mitigation efforts.

SURVEILLANCE AND EPIDEMIOLOGIC STUDY DESIGNS

As noted previously, health outcomes can be linked to exposure data by various epidemiologic methods. A brief overview of these methods follows. Various introductory and advanced textbooks, as well as review articles on epidemiologic methods, can be consulted for more comprehensive coverage of this topic and for detailed definitions of various epidemiologic terms used in this chapter and report (e.g., Gordis, 2000; Last, 2001; Lavori and Kelsey, 2002; Matthews, 2000; Meinert, 1986; Rothman and Greenland, 1998; Rothman, 2002; Schlesselman, 1982).

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
×

Surveillance

Modern public health surveillance of disease was defined by Langmuir (1963) as “the continued watchfulness over the distribution and trends of incidence through the systematic collection, consolidation and evaluation of morbidity and mortality reports and other relevant data.” It is now standard practice to add to this definition the concept of applying these data to prevention and control of disease.

The steps in surveillance include the systematic collection of data, analyses to produce statistics, interpretation to provide information in a timely manner, actions taken as a result of the data, and continued surveillance to evaluate the success of the actions taken. Guidelines for evaluating surveillance systems have been proposed by the Centers for Disease Control and Prevention (CDC, 2001).

Epidemiologic Study Designs

Epidemiologic studies fall into two general categories: (1) experimental studies (e.g., randomized controlled intervention or clinical trials) in which investigators control the conditions of exposure in the study and (2) observational studies (e.g., cohort, case-control, cross-sectional, and ecologic studies) in which investigators do not control the exposure or most other aspects of the process being studied.

Of the epidemiologic studies, randomized controlled trials provide the strongest epidemiologic evidence of an etiologic association between exposure and outcome, followed in decreasing order by cohort studies, case-control studies, cross-sectional studies, and ecologic studies.

Randomized Controlled Trial

This epidemiologic experimental design is regarded as the most scientifically rigorous method of hypothesis testing available. Subjects are randomly allocated into two groups, one that will receive an experimental treatment or intervention and the other that will not. Randomization tends to produce comparability between the two groups with respect to factors that might affect the health outcome being studied and, thus, to minimize the potential for confounding variables.1 Additional objectivity is provided when subjects, investigators, and statisticians analyzing the data are unaware of the subject’s allocation to a particular treatment or intervention (known as randomized triple-blinded trials). The scien-

1  

Confounding variables (“confounders”) are variables that can alternatively cause or prevent the outcome of interest in an epidemiologic study and are associated with the factor under investigation. As such, confounding variables may be due to chance or bias, and unless adjusted for, their effects cannot be distinguished from those factors being studied.

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
×

tific rigor of this study design is its chief advantage, while its cost, often in the millions of dollars, is its greatest disadvantage. Therefore, randomized controlled trials are generally used only when a well-defined hypothesis is being tested.

Randomized controlled trials have additional benefits. They provide a temporal association between the exposure and the health outcome, which is one measure of causality, because the exposure precedes the outcome. They also allow for the calculation of incidence rates of disease in each group (i.e., the occurrence of a certain disease or health outcome in a group or population over a specified period of time) and their relative risk rather than being limited to calculations of odds ratios. As defined in A Dictionary of Epidemiology, edited by Last (2001), a relative risk (RR) or risk ratio is “the ratio of two risks, usually exposed/ not exposed.” The odds ratio (OR) is defined differently according to the situation (e.g., calculation of odds of exposure or odds of disease). As defined in Last (2001), “The exposure-odds ratio for a set of case-control data is the ratio of the odds in favor of exposure among the cases to the odds in favor of exposure among non-cases” and “the disease-odds ratio for a cohort or cross-sectional study is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed.” Problems associated with randomized control trials include noncompliance, participant dropout, and generalizability of results.

A related type of experimental design is a community intervention trial in which the exposure is assigned to groups of people rather than singly. This type of experiment is often used to study environmental exposures. Most community intervention trials do not employ random assignment for the experimental treatment; rather, they use a cross-over design (i.e., before and after treatment) where the community serves as its own control.

Cohort Study

A cohort is defined as a group of persons who are followed over a period of time and usually includes individuals with a common exposure. A cohort study involves measuring the occurrence of disease within one or more cohorts that have differing exposures during a certain period of follow-up. John Snow’s study of the cholera outbreak in 1854 (see Chapter 1 for a brief description; Snow 1854) is an elegant example of a cohort study. Cohort studies can be prospective (exposure information is recorded at the beginning of the follow-up and the period of time at risk is forward in time) or retrospective (cohorts are identified from recorded information and the follow-up time occurred before the beginning of the study). Cohort studies have several advantages. They allow for the association of multiple health outcomes or diseases, or multiple endpoints within the progression of one disease, along with the exposure of interest. Like randomized controlled trials, cohort studies provide a temporal association between exposure and health outcome. Finally, incidence rates of disease in the cohorts being assessed and their relative risk can also be calculated.

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
×

Cohort studies are subject to several types of potential bias, including bias in the selection of the cohorts’ exposure, bias in assessment of the health outcome, and bias if the two cohorts have differing response rates. A cohort design is generally selected when there is good evidence of an association of a health outcome with a certain exposure and when the exposure is relatively rare but the incidence of disease among the exposed group is high. Attrition of the study population is minimized when the time between exposure and disease is short. Although not as costly as a randomized experiment, cohort studies are generally more expensive that other types of epidemiologic designs. As with most epidemiologic studies, cohort studies are subject to confounding. Known confounding factors can be controlled for in the analysis of the data, but unknown confounders are by their nature impossible to adjust for in the analysis.

Case-Control Study

This type of study aims to achieve the same goals as the cohort study while minimizing the need to obtain information on exposure and outcome from large populations. Samples are taken from the source population to reduce the number of study participants. Properly designed and conducted, case-control studies provide information that is similar to what could be collected from a cohort study but at considerably less cost and time. In this study design, the investigator selects individuals with the health outcome of interest (cases) and appropriate individuals without the health outcome (controls), collects information regarding their past exposure, and then compares the rates of exposure of the two groups. Issues to be considered when using this study design include the ascertainment of cases of disease (e.g., diagnostic criteria, population source, incident or prevalent cases) and the selection of appropriate controls (i.e., should controls be comparable to cases in all respects other than having the disease, and how many variables between cases and controls should be matched?). A case-control study design is often used when investigators want to determine the association of a health outcome, especially a rare one, with multiple rather than single exposure factors.

Case-control studies are subject to several biases, including recall bias (i.e., cases might be more likely to remember their past exposure than controls), selection bias, and nonresponse bias. Case-control studies suffer from the same problems with confounding factors as cohort studies. Another disadvantage of case-control studies is the inability to calculate incidence rates and their differences and ratios (e.g., relative risks); investigators can calculate only the ratio of incidence or prevalence rates or risks (e.g., odds ratios; see previous discussion of relative risk and odds ratio).

Cross-Sectional Study

This type of study provides a snapshot of the status of a target population

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
×

with regard to exposure status, health outcome, or both at a specific point in time. Cross-sectional studies attempt to enumerate the population and assess the prevalence of various characteristics. This design is characterized by the fact that only one set of observations is taken from each person. Although it cannot measure disease incidence because information across time is not available, disease prevalence can be assessed. Cross-sectional studies often are the first type of epidemiologic study conducted to determine the association between a health outcome and several possible exposure variables. As the hypothesis to be tested is refined, investigators typically progress to one of the other study designs. In some instances, however, cross-sectional surveys are conducted repeatedly over long periods as a form of disease surveillance system.

Ecologic Study

An ecologic study, also known as an aggregate study, compares groups rather than individuals. This design is most often used when individual-level data are missing. Although ecologic studies are relatively easy and inexpensive to conduct, their results are often difficult to interpret. Ecologic studies are used to study environmental exposures because it is difficult to accurately measure relevant exposures or doses at the individual level for large numbers of persons. In addition, exposure levels may vary little within a study area. The major limitation of ecologic analyses is the so-called ecologic bias in which the expected ecologic effect fails to accurately represent the biologic effect at the individual level. Robinson (1950) was the first to describe mathematically how ecologic associations could differ from the corresponding associations at the individual level. This phenomenon has become widely known as the ecologic fallacy.

Other Types of Studies

Some epidemiologic studies can be considered a specific type of the aforementioned study designs or use methods that incorporate multiple elements of these basic study designs. Longitudinal time series studies and seroprevalence studies are two such examples. Longitudinal time series are cohort-type epidemiologic studies that correlate exposure variables of interest (e.g., an environmental indicator such as water turbidity or the presence of a waterborne pathogen like Cryptosporidium parvum in water) with health outcomes (e.g., a clinical measurement such as an immunologic marker of exposure in a serologic specimen or a direct measurement such as occurrence of diarrhea) over a specified period of time. These studies incorporate temporal factors in their analyses with exposure occurring before the health outcome. The need to include the (most) appropriate time lag between measurement of the exposure and health outcome make these analyses complex and difficult to successfully accomplish as well as making interpretation of the results difficult at times. However, these studies can

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
×

provide good epidemiologic associations between exposures and adverse health outcomes.

Seroprevalence studies are a specific type of cross-sectional study design. These studies measure the prevalence of a serologic marker in study participants as the health outcome of interest. Serologic markers can be difficult to interpret, however, because their measurements represent historical exposure and it is not always clear when and for how long the selected marker is present after exposure to a pathogen of concern. In addition, there may be multiple markers to choose from (e.g., circulating antibodies to several antigens), which further complicates interpretation of results. Nevertheless, seroprevalence studies are useful in determining population exposure to a pathogen even when the pathogen itself cannot be detected. Lastly, measuring seroprevalence is especially useful in investigations of waterborne disease outbreaks because it can establish that individuals were previously exposed and infected.

HISTORICAL REVIEW AND CURRENT STATUS OF HEALTH EFFECTS ASSESSMENT

The following section provides an overview (historical and current) of the most salient epidemiologic assessments of health effects associated with drinking water and recreational water exposure. Please refer to the previous section for a review of the surveillance and epidemiologic terms and methods used in the health assessments described below.

U.S. National Waterborne Diseases Outbreak Surveillance System

Surveillance for outbreaks associated with drinking water and recreational water has been going on since 1920 (Craun, 1986). The CDC, the U.S. Environmental Protection Agency (EPA), and the Council of State and Territorial Epidemiologists (CSTE) have maintained a collaborative surveillance system of waterborne disease outbreaks (WBDOs) since 1971 (see also Chapter 1). The National Waterborne Diseases Outbreak Surveillance System (WBDOSS), located at CDC, collects data regarding outbreaks associated with drinking water and recreational water. Moreover, in recent years (1999-2000), the WBDO surveillance system has also provided data on outbreaks that occurred as a result of occupational exposure to water. The primary objective of collecting outbreak data is ultimately to reduce the occurrence of WBDOs by characterizing the epidemiology of the outbreaks, identifying the etiologic agents, and determining the reasons for the occurrence. Results from these efforts provide the opportunity to issue public health prevention and control messages.

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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Characteristics of the Surveillance System

State, territorial, and local public health agencies are responsible for detecting and investigating WBDOs. As a federal agency, CDC participates in outbreak investigations only by invitation from a state or territorial epidemiologist or if an outbreak involves multiple states. Reporting is voluntary and passive, and varies by state. States and territories report their outbreaks annually on a standard (hard copy) form (CDC Form 52.12), and CDC compiles, analyzes, and publishes the data. Since 1989, when responsibility for the surveillance system was moved to CDC’s Division of Parasitic Diseases, the data have been published every two years as a Morbidity and Mortality Weekly Report (MMWR) Surveillance Summary (Barwick et al., 2000; Herwaldt et al., 1991; Kramer et al., 1996; Lee et al., 2002; Levy et al., 1998; Moore et al., 1993). Both the surveillance system’s submitted hard copy report forms and the electronic database reside at CDC.

Two major categories of data are reported on the forms: (1) epidemiologic data such as type of exposure; number of persons exposed, ill, and hospitalized; number of fatalities; symptoms; etiologic agent; and results from clinical laboratory data; and (2) environmental data such as the type of water system involved, results from water testing, and factors that contributed to contamination of the water. CDC contacts the state’s environmental agency if additional information regarding source water, treatment, or supply is needed to flesh out the investigation and to work through the issues that led to the contamination. Completion rates for the report forms vary tremendously by outbreak investigation, as well as by the intensity and scope of the investigation.

Unlike most surveillance systems, the unit of analysis in WBDOSS is an outbreak rather than an individual case of a specific disease. Two major criteria must be met for an event to be classified as an outbreak: (1) at least two persons must have experienced a similar illness after consumption of a common source of drinking water or after exposure to water used for recreational purposes and (2) epidemiologic data must implicate water as the probable source of the illness. However, the stipulation that at least two persons be ill is waived for single cases of laboratory-confirmed primary amoebic meningoencephalitis (PAM; see also Chapter 3) and for single cases of chemical poisoning if water quality data indicate contamination by the chemical. An outbreak that meets both criteria will be included in the surveillance system whether the etiologic agent is infectious, chemical, or unidentified.

WBDOs are classified (Class I-IV) according to the strength of the evidence implicating water. Epidemiologic data are weighted more heavily than water quality data, and outbreaks that are reported without supporting epidemiologic data are excluded from the surveillance system (see Table 2-1).

In addition, each drinking water system associated with an outbreak is classified by the following types of problems: untreated surface water, untreated groundwater, treatment deficiency (e.g., inadequate disinfection), distribution

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
×

TABLE 2-1 Classification of Investigations of Waterborne Disease Outbreaks in the United Statesa

Classb

Epidemiologic Data

Water Quality Data

I

Adequatec

a) Data were provided about exposed and unexposed persons; and

b) Relative risk or odds ratio was ≤ 2, or the P-value was <.05

Provided and adequate historical information or laboratory data such as the history that a chlorinator malfunctioned or a water main broke, no detectable free-chlorine residual, or the presence of coliforms in the water

II

Adequate

Not provided or inadequate (e.g., stating that a lake was crowded)

III

Provided, but limited

a) Epidemiologic data provided did not meet the criteria for Class I; or

b) The claim was made that ill persons had no exposures in common besides water, but no data were provided

Provided and adequate

IV

Provided, but limited

Not provided or inadequate

aOutbreaks of Pseudomonas and other water-related dermatitis and single cases of primary amoebic meningoencephalitis or of illness resulting from chemical poisoning are not classified according to this scheme.

bBased on the epidemiologic and water-quality data provided on CDC Form 52.12.

cAdequate data were provided to implicate water as the source of the outbreak.

SOURCE: Adapted from Lee et al., 2002.

system deficiency (e.g., cross-connection), and unknown or miscellaneous deficiency (e.g., contamination of bottled water).

Usefulness of the Surveillance System

Outbreak data gathered through this surveillance system are useful for identifying deficiencies in providing safe drinking water and recreational water, evaluating the adequacy of current regulations for water treatment, and monitoring water quality. In addition, outbreak data are used to determine or update the biology and epidemiology of etiologic agents and to influence research priorities.

However, the WBDO surveillance system does not consistently provide information that would help researchers link indicator and pathogen data with health outcome data because the collection of water quality data is not required for inclusion of an outbreak in the system. In addition, the utility of coliform data as an indicator of outbreak vulnerability of public water systems has come into question in a recent study by Nwachuku et al. (2002). That study compared Total

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
×

Coliform Rule (TCR; see also Table 1-1) violations for water systems that had and had not reported an outbreak from 1991 to 1998. Their findings suggested that the TCR is not able to identify those water systems that are vulnerable to an outbreak. The authors of that study suggest that source water be examined using a wide variety of indicators because simply monitoring treated drinking water for one indicator, most often coliforms, will not provide a useful measure of the water’s overall microbial quality. The difficulty of collecting water samples in a timely manner is a complicating factor in attempts to epidemiologically link contaminated water with adverse health outcomes.

Adding to the difficulty of linking water quality data to health outcome data is the fact that health agencies and environmental agencies are separate in approximately 70 percent of states, and this probably holds true at county and local levels as well (Lynn Bradley, Association of Public Health Laboratories, personal communication, 2003). Thus, responsibility for investigating waterborne outbreaks will rest with either the health staff or the environmental staff. Therefore, the thoroughness of the epidemiologic versus the environmental components of any outbreak investigation will vary with each local or state agency. Better coordination between the two components of a waterborne disease investigation would increase the completeness of investigations. In this regard, participants in a recent colloquium on the burden of gastrointestinal illness recommended a team approach to outbreak investigations and standardized protocols and case definitions (Payment and Riley, 2002).

The importance of, and approaches to, waterborne disease surveillance and other epidemiologic methods of estimating waterborne disease burdens, etiologies, and causes have been addressed by the World Health Organization (WHO; Fewtrell and Bartram, 2001). Several chapters of that WHO report describe approaches and limitations of acquiring, interpreting, and applying epidemiologic information on waterborne disease to prevention and control measures. The report also discussed the development of water quality criteria, guidelines, and standards. Standardized protocols for waterborne outbreak investigations, especially for large outbreaks, could help ensure comprehensive investigations that include the collection of epidemiologic, clinical, laboratory, and environmental data. Such investigations would allow researchers to maximize the information obtained and provide opportunities to associate various exposure factors with health outcomes.

Representativeness of Outbreaks Reported to the WBDO Surveillance System

Many factors affect the likelihood that a waterborne outbreak will be recognized and investigated; such factors lead to concerns about the representativeness of WBDOs that are reported, including the following (Lee et al., 2002):

  • The larger the outbreak, the more likely it is to be detected over background incidence of illness or related symptoms.

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
×
  • The more severe the illness (e.g., bloody diarrhea caused by Escherichia coli O157:H7), the more likely the outbreak will be detected.

  • The public’s awareness that an outbreak is occurring will more readily lead people to call their local health department to report an illness.

  • A clinician’s specific interest in an agent (e.g., Cryptosporidium parvum at a time when this protozoan was not well known) will help ensure that a request for laboratory testing to identify the agent is more likely.

  • State and private laboratories vary in their routine testing practices for pathogens in stool specimens, making the detection of any pathogen more or less likely (e.g., Cryptosporidium parvum may not be included automatically in a request for routine ova and parasite testing of a fecal specimen).

  • Local and state health departments have limited budgets and allocate resources according to the perceived health risks to their communities.

In general, outbreaks with high attack rates (i.e., the cumulative incidence of infection in a group observed during an epidemic) or a large number of cases of illness associated with severe symptoms in a state that has had previous waterborne outbreaks are likely to be recognized. Outbreaks that are more likely to be missed include those that have low attack rates, are associated with mild symptoms, and are caused by an etiologic agent that is not easily identified such as a virus. It is important to note that a large proportion of identified outbreaks to date have occurred in small communities. This indicates that increases in outbreak-related cases of illness in larger communities and cities might be missed because such cases are typically reported to a much wider variety of physicians and laboratories.

Sensitivity of the Surveillance System and Underreporting

The sensitivity of the WBDO surveillance system (i.e., the probability that an actual outbreak will be identified correctly, reported to CDC, and recorded into the surveillance database) is unknown because the actual (total) number of WBDOs cannot be determined. However, the sensitivity of the system is probably low because of underreporting of WBDOs, likely caused by lack of recognition that an outbreak is occurring or has already occurred. The multiple sequential barriers that can exist to reporting cases of outbreak-related illness are listed below:

  • person gets infected when exposed to agent;

  • person becomes symptomatic;

  • person seeks medical care;

  • health care worker orders a laboratory test;

  • person provides the requested specimen (e.g., stool);

  • laboratory tests for the specified agent;

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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  • test result is positive;

  • positive result is reported to the health department;

  • health department reviews and analyzes the reports in a timely manner;

  • health department concludes that an outbreak might be occurring; and

  • health department investigates the potential outbreak.

Enough nonoccurrences or failures at any of these steps could result in a missed WBDO.

To complicate matters, standardized clinical and environmental laboratory methods that are both sensitive and specific are lacking for many viruses, and routine testing for parasites in fecal samples is not always done. For example, the incubation period for parasitic diseases such as cryptosporidiosis averages 7 days and can be as long as 14 days, making the association between illness and water exposure much more difficult.

Planned Improvements to the Surveillance System

The hard copy form used to report WBDOs to the WBDOSS was revised recently to allow for more specific reporting of water quality data (e.g., turbidity, total and fecal coliforms, other indicators of waterborne pathogens as needed). While states sometimes report finished water quality data, inclusion of source water quality monitoring data for a variety of indicators would likely contribute important information. More options are provided on the outbreak reporting form for listing the types of problems and deficiencies encountered in drinking water systems (e.g., lack of filtration, lack of backflow prevention, cross-connection, negative pressure) and in recreational water settings (e.g., heavy bather density, animal or human fecal contamination). The system will expand the types of outbreaks that it includes, such as outbreaks of legionellosis and wound infections associated with exposure to recreational water.

As a result of these recent and planned changes, CDC will interact more actively with state waterborne disease coordinators to make them aware of the report revisions. CDC also plans to use this opportunity to review problems with outbreak reporting and to emphasize the need for collecting water quality data in addition to the epidemiologic data that are routinely collected.

Epidemiologic Studies of Diseases Attributed to Drinking Water

For drinking water, experimental and observational epidemiologic studies have focused on determining if there is an association between water consumption and adverse health outcomes, especially gastrointestinal illness. There has been an ongoing debate in the United States about the extent to which infectious diseases may be transmitted to humans through drinking water that meets federal standards for water quality. These concerns have been heightened by: (1) the

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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continuing occurrence of waterborne disease outbreaks (see Figures 1-1, 1-2, and 1-3); (2) two outbreaks associated with public water systems that met Safe Drinking Water Act (SDWA) standards (Goldstein, 1996; Mac Kenzie et al., 1994) but resulted in a number of deaths; (3) a 2002 outbreak of primary amoebic meningoencephalitis caused by Naegleria fowleri associated with untreated groundwater;2 and (4) the findings of Payment et al. (1991, 1997; see more below and Chapter 1), which suggested that between 14 and 40 percent (depending on population group and water exposure) of gastrointestinal illness in a community might be attributable to waterborne pathogens.

Various methods can be used to estimate the strength of an association between an exposure variable and a health outcome variable, and EPA and CDC are in the process of developing a congressionally mandated (i.e., SDWA Amendments of 1996) national estimate of waterborne disease occurrence. As noted in Chapter 1, the congressional language “waterborne disease occurrence” has been interpreted to mean that the focus of the study should be on “gastrointestinal disease attributable to municipal drinking water.” A review of the epidemiologic studies that have and will provide data components (attributable fractions3 from select water systems and gastrointestinal rates in the general population) to be used in developing the national estimate are summarized below.

The Canadian Intervention Trials

As discussed in Chapter 1, at the time that Payment and colleagues (1991) designed their first intervention trial, it was generally thought that drinking water meeting Canadian water quality standards posed a minimal health risk to consumers. However, the advent of more sensitive detection methods for waterborne viruses and parasites, coupled with the continued occurrence of waterborne outbreaks, raised some doubts as to whether municipal waters were free of microorganisms that could be pathogenic to humans. In addition, there was concern that endemic waterborne disease might be occurring without being recognized. For these reasons, Payment and colleagues designed a randomized trial to measure the rates of gastrointestinal illness related to the consumption of tap water that met then current water quality standards. However, the source of the tap water used in the study was surface water contaminated with human sewage. It was estimated that 35 percent of the reported gastrointestinal illness among tap water drinkers was related to consumption of the drinking water and was thus prevent-

2  

See http://www.uswaternews.com/archives/arcrights/3attfil7.html and http://www.maricopa.gov/public_health/docs/alerts/newsrelease-nov1102f.pdf for further information.

3  

For the purpose of this report, the term “attributable fraction” refers to the proportion of all cases that can be explained by (attributed to) a particular exposure (see Last, 2001, for further information on how this term is defined and used in epidemiology).

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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able. The study also included testing of raw source water and finished treated water for several indicators of water quality, including turbidity, chlorine, total bacteria, total and fecal coliforms, Pseudomonas aeruginosa, Aeromonas hydrophila, Clostridium perfringens, and human enteric viruses and bacteriophages. Despite the association of tap water with gastrointestinal illness, researchers did not find any correlations between illness and any of the physical, chemical, and microbial indicators measured.

As the debate continued about whether coliform-free drinking water was also pathogen-free, Payment and colleagues followed up their first intervention trial with a second randomized trial in the same study area (Payment et al., 1997). Large-volume analyses of raw source water were conducted for human enteric viruses, Giardia lamblia, Cryptosporidium parvum, Clostridium perfringens, and coliphages. Analyses were also conducted in post-filtration, pre-disinfection, and finished treated water. The tap water met or exceeded then-current water quality standards, and the distribution system was in compliance with regulations for coliforms and chlorine residual. The results of this trial indicated that 14 to 40 percent (depending on the age group and study assignment group) of gastrointestinal illness was attributable to tap water that met water quality standards. Furthermore, the results indicated that the water in the distribution system appeared to be partly responsible for the illnesses.

The Australian Intervention Trial

As a result of the two Payment studies and based on modeling data of Cryptosporidium oocysts obtained from quantitative microbial risk assessment (QMRA; discussed later) (Haas et al., 1996), new public health concerns were raised about the microbiological safety of drinking water in developed countries and the possibility that substantial endemic waterborne disease was going unrecognized. These concerns led to a randomized controlled intervention trial in Melbourne, Australia (Hellard et al., 2001). These researchers sought to improve on the previous trials by Payment and colleagues by incorporating double blinding into the study design (i.e., participants and investigators were unaware of the participants group assignment). Source water for the study area was obtained from uninhabited and protected forest catchments without farming or recreational water activity.

Six hundred households were randomly allocated to receive either a treatment device or a sham device and were followed for 68 weeks. This trial did not find a statistically significant difference between the rates of gastrointestinal illness in each group. Pathogens in fecal specimens were not found to be more common in the group that received the sham device. Routine water quality monitoring was performed by the water utility at customer properties. Water samples were tested for total and fecal coliforms, heterotrophic plate count bacteria (HPCs), and free and total chlorine. A composite sample from the four water

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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mains that supplied the study area was collected weekly and analyzed for Giardia lamblia, Cryptosporidium parvum, Aeromonas, Clostridium perfringens, and Campylobacter. One possible explanation for the differing results between the Hellard and Payment trials is the quality of the source water. This raises the issue of generalizability of results from studies conducted in specific populations and geographic locations using specific types of water systems.

The U.S. Intervention Trials and Observational Studies

As mentioned previously, EPA and CDC decided that one method of developing a national estimate of endemic waterborne disease would be to obtain attributable fractions from controlled experiments and apply them to incident gastrointestinal illness rates in general populations determined from observational studies, such as cross-sectional surveys.

Pilot Water Evaluation Trials (Pilot WET and HIV WET) Two trials were designed in different populations to minimize the problems encountered in the previous intervention studies. The objectives were to assess (1) the effectiveness of triple blinding to group assignment (i.e., participants, investigators, and analysis team); (2) the effectiveness of the treatment device; (3) the logistical obstacles that could be encountered in conducting the trial; (4) the effectiveness of data collection tools (e.g., health diary); and (5) the ability to collect fecal and serologic specimens and to test for various enteric bacteria, viruses, and parasites.

In the first pilot trial, the study population was composed of healthy adults and children living in a northern California community supplied by surface water and included 77 households (Colford et al., 2002). The water treatment plant serving the study area used conventional treatment with chloramination, and the finished water met all federal and state drinking water standards. Household tap water was tested in a subsample of the households for HPCs, total coliforms, copper, lead, and sulfites. Study results showed that participants could successfully be blinded to their treatment assignment. While not a primary objective of the study because of its small sample size, incidence rates of gastrointestinal illness were compared between the two groups, and the attributable fraction—although not statistically significant (most likely because of a lack of statistical power)—was unexpectedly found to be 24 percent. No significant differences were found in water consumption patterns between the two groups.

The second pilot trial was designed with the same objectives as the first except for the target population, which was an HIV-infected cohort. Immunocompromised persons such as those with HIV are at increased risk of infection and severity of illness from pathogenic organisms because their immune systems are less able to protect them. This study population (50 HIV-infected patients) was from a northern California community that receives approximately 80 percent of its water from the largest unfiltered surface water supply on the

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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West Coast. Household tap water was analyzed for HPCs, copper, lead, sulfate, and residual chlorine. This study has been completed and an attributable fraction has been calculated that could be applied to incidence rates of gastrointestinal illness in immunocompromised populations when calculating estimates of waterborne diseases (the manuscript has been submitted for publication and is currently under review [Deborah Levy, CDC, personal communication, 2004]). In addition, in preparation for this trial, a cross-sectional survey was conducted to determine the prevalence of gastrointestinal illness and drinking water consumption patterns in the HIV-infected study population. Forty-seven percent of respondents reported a gastrointestinal illness in the seven days before being surveyed (Eisenberg, 2002a). While drinking boiled or filtered water was not associated with diarrhea, those who drank bottled water were at significantly increased risk. Extending their work from one HIV clinic to two additional clinics, the researchers found that the risk of diarrhea was lower among those consuming boiled water, although this finding was not statistically significant and the relative risk of diarrhea for “always” versus “never” drinking bottled water was also nonsignificantly elevated (Eisenberg, 2002b).

Big WET and Nested Epidemiologic and Water Quality Studies Big WET is a full-scale, randomized, triple-blinded, controlled intervention of drinking water treatment. The study was conducted from October 2000 through June 2002 in Davenport, Iowa, a community that derives its drinking water solely from surface water. The water treatment plant serving the study area used conventional treatment with chloramination, and the finished water met all federal and state drinking water standards. The primary objective of this trial was to determine the incidence of gastrointestinal illness in groups randomly assigned to receive either a water treatment or a sham device and to calculate the fraction of the gastrointestinal illness attributable to consumption of the drinking water. Four hundred households, including adults and children, were monitored for one year.

To maximize the benefit of a large-scale trial, several nested studies were included:

  1. Because a secondary objective of the trial was to gather data that would aid in the formulation of a national estimate of waterborne endemic disease, a cross-sectional telephone survey was administered to 400 randomly selected persons once a quarter for the 12-month follow-up period. The survey questionnaire, modeled after CDC’s FoodNet survey (described below), collected information about water consumption patterns in and out of the home, swimming activities, symptoms of gastrointestinal illness, and burden of illness as measured by missed school, work, and recreational activities. Community surveillance data are increasingly being used in studies of gastrointestinal illness but have not been validated against data collected from individual reporting of illness. Thus, Big WET

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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provided a unique opportunity to compare gastrointestinal illness reports from daily health diaries and from a random digit dialing telephone survey.

  1. As a result of unexpected severe flooding during the study period, participants completed an additional survey related to exposure to flood water. The objectives of this study were to determine whether rates of gastrointestinal illness were elevated during the flood and whether contact with flood water was associated with an increased risk of gastrointestinal illness. The results of this study have been accepted for publication in the American Journal of Epidemiology (Deborah Levy, CDC, personal communication, 2004).

  2. A water sampling program was implemented and funded by the American Water Works Association Research Foundation (AWWARF Project #2580). This study was designed to determine whether a significant relationship exists between water quality indicators and gastrointestinal illness and, in the event of a difference in gastrointestinal rates in the intervention trial, to determine the most likely source of water contamination. Throughout the intervention trial, raw water, effluent water, and water entering the distribution system were tested for common water quality indicators and waterborne pathogens. These indicators and pathogens included total and fecal coliforms, E. coli, Giardia lamblia, Cryptosporidium parvum, Clostridium perfringens, Bacillus subtilis, somatic and male-specific coliphage, HPCs, culturable enteric viruses, and algae, as well as water pH, temperature, turbidity, alkalinity, chlorine, phosphate, and hardness. Water from household taps was tested for total coliforms, HPCs, pH, temperature, turbidity, and total chlorine. The AWWARF project report has been completed and is in the process of being published (Deborah Levy, CDC, personal communication, 2004).

  3. EPA provided additional funding to conduct a brief plumbing survey of a subsample of households participating in the trial to ensure that frequency of cross-connections within the households could be controlled for in analyses of the association between water consumption and gastrointestinal illness.

Big WET and all of the nested studies have been completed. Primary analyses of the data from the trial have been completed, and the manuscripts are currently being written and submitted for publication (Deborah Levy, CDC, personal communication, 2004). The primary results of the Big WET study were presented at the annual conference of the International Society of Environmental Epidemiology in Perth, Australia on September 26, 2003 (Colford et al., 2003). The study did not find a reduction in gastrointestinal illness after the use of a treatment device designed to be highly effective in the removal of microorganisms from tap water. Secondary epidemiologic, clinical, and environmental analyses are being conducted and should be completed in early 2004. Analyses linking data from Big WET trial with data from the nested studies are ongoing and the flood-related manuscript has already been accepted for publication. Although this intervention trial was expensive to conduct, a variety of epidemiologic, clinical,

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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and environmental issues were addressed because of the possibility of nesting multiple smaller studies within the larger study. As demonstrated with Big WET, and given the lack of funding often encountered, fewer but more comprehensive epidemiologic studies rather than multiple smaller studies that focus only on one or two issues should be funded and conducted when working within a fixed or constrained budget, thus providing a better cost-benefit ratio. Budgetary constraints notwithstanding, the same principles of thorough epidemiologic investigation apply to epidemiologic studies as to outbreak investigations. That is, the need to collect epidemiologic, clinical, laboratory, and environmental (both pathogens and indicators whenever feasible) data.

FoodNet Cross-Sectional Survey The Foodborne Diseases Active Surveillance Network (FoodNet) is the principal foodborne disease component of CDC’s Emerging Infection Program (EIP). FoodNet is a collaborative project of CDC,4 10 EIP states,5 the U.S. components, including an active laboratory-based surveillance; a survey of clinical laboratories, physicians, and a randomly selected population in the EIP catchment areas; and epidemiologic studies.

The survey of the EIP population is relevant to the development of a national estimate of waterborne disease. Before FoodNet, few studies provided reliable estimates of population rates of gastrointestinal illness (Hodges et al., 1956; Monto and Koopman, 1980). The FoodNet population survey collects information on recent gastrointestinal illness and will serve as one source of the incidence rates of gastrointestinal illness in the population that are needed to calculate the national estimate. Attributable fractions obtained in the intervention trials will be applied to these population rates. Population-based estimates of the burden of gastrointestinal illness in the United States calculated from FoodNet 1996-1997 data were published in 1999 and again in 2002 (Herikstad et al., 2002; Mead et al., 1999).

Community Intervention Trials As part of the national estimate of endemic waterborne disease, EPA has conducted three intervention trials in communities that upgraded their treatment plant operations (e.g., adding filtration). The design was a matched pre- and post-community intervention (i.e., improved water treatment). The target population is randomly selected from the community, and all participants completed health diaries and provided serum and fecal specimens. The primary objective is to compare incident rates of gastrointestinal illness before and after the intervention, while the second objective is to compare

4  

For further information about FoodNet, see http://www.cdc.gov/foodnet/.

5  

California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee.

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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seroprevalence rates for Cryptosporidium parvum for the two periods. EPA already has water quality data for these water systems collected under the Information Collection Rule (ICR; see Table 1-1). Additional information about these trials is provided in Table 2-2. Results from these community interventions will provide, like their counterparts in the experimental interventions, waterborne attributable fractions that can be applied to incident gastrointestinal rates for target populations of interest. Furthermore, several other ongoing studies that use a variety of epidemiologic designs and measure the association between water consumption and gastrointestinal illness are also summarized in Table 2-2.

Other Epidemiologic Studies

Other observational studies have been conducted to address the association between drinking water consumption and illness and they are briefly noted below. Details of these studies can be found in the original published manuscripts, which are referenced. Several time series studies by Schwartz and Levin (1999) and Schwartz et al. (1997, 2000) attempted to show an association between water turbidity and illness. These studies are difficult to interpret because of concerns about the temporal associations as well as the reliability of the turbidity measurements. Naumova et al. (2003) used time series analyses to study the association between emergency room visits and hospitalization caused by gastrointestinal illness and drinking water turbidity before and during the Milwaukee waterborne Cryptosporidium outbreak of 1993 (see also Chapter 1).

EPA and AWWA have conducted or funded several studies that compared seroprevalence rates of antibodies to Cryptosporidium parvum in paired cities with different types of source water and water systems (AWWA, 1999; Frost et al., 2001, 2002). General epidemiologic descriptions of time series studies and seroprevalence studies are provided near the beginning of this chapter.

U.S. National Estimate of Waterborne Disease Occurrence—Current Status and Future Direction

The SDWA amendments of 1996 (1458[d]) set a time line for the development of a national estimate of waterborne disease occurrence at five years after its promulgation in August 1996. However, because of variables involved in designing and conducting epidemiologic studies, the effort will take longer to complete. EPA and CDC already have developed the framework for calculating the estimate using waterborne attributable fractions and incidence rates of gastrointestinal illness, and are currently waiting for results from the trials. In the meantime, EPA work is focused on developing a model for characterizing water systems according to microbial risk while CDC efforts are focused on analyzing FoodNet water data and waterborne disease outbreak data. An additional component that the two agencies would like to incorporate into the calculation of the national

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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estimate, if feasible, is seroprevalence of Cryptosporidium parvum from the fourth cycle (1999-2000) of the National Health and Nutrition Examination Survey (NHANES IV).6 CDC conducts NHANES periodically and is the only national source of objectively measured health data that can provide estimates of both diagnosed and undiagnosed medical conditions in the population. Data are collected for biomedical research, public health, tracking of health indicators, and policy development through physical examinations, clinical and laboratory tests, and interviews. Seroprevalence rates have been calculated for target populations across the United States, and CDC will attempt to determine if there is an association between these rates and the type of water system in the community from which the population was selected (EPA will provide the water system information).

The development of a national estimate of gastrointestinal illness that can be attributed to municipal drinking water is expected to be an evolving effort. The first few studies were conducted in communities with surface water systems because these were thought to be more vulnerable to contamination and therefore more of a public health risk. As a result, information currently is lacking for groundwater systems. However, EPA recently funded a study in a groundwater community in Florida and has plans to fund more through their Science to Achieve Results (STAR) grants program.7 The primary objective of the Florida study is to estimate the risks of endemic gastrointestinal illness associated with consumption of conventionally treated groundwater and to determine the relative contributions of source water quality, treatment efficacy, and distribution system vulnerability to endemic waterborne disease. The study design proposed was a 12-month, double-blinded, randomized intervention trial that will include 900 households and will measure rates of gastrointestinal illness in groups with drinking water that receives different levels of treatment.

The national estimate of endemic waterborne disease will be updated and refined as data become available from the ongoing as well as new studies and additional data sources are mined (Deborah Levy, CDC, personal communication, 2004). Potential sources of these data include surveillance databases, additional epidemiologic studies, additional populations and geographic sites, systematic reviews and meta-analyses, and public health and microbial risk assessment. Furthermore, the estimate will be expanded, ideally to include other waterborne illnesses (e.g., respiratory illness) and other types of water (e.g., ambient and treated recreational waters, private wells). Finally, collaboration with WHO would expand the effort and include developed and developing countries across the world.

6  

For further information about NHANES, see http://www.cdc.gov/nchs/nhanes.htm.

7  

For further information about EPA’s STAR grants program, see http://es.epa.gov/ncer/grants/.

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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TABLE 2-2 Summary of Key Characteristics of Select Epidemiologic Studies Associating Drinking Water with Health Outcomes

Study Sponsor/Primary Institution

Study Design

Geographic Location—Water System

Population

Study Size

National Institutes of Health/University of California, Berkeley

Randomized triple-blinded intervention trial

Sonoma and Santa Rosa, California—mixed water system

Elderly

500 households

CDC/Tufts University

Longitudinal time series

Lowell and Newton, Massachusetts—surface water systems, one with filtered river water and one unfiltered from a partially protected watershed

Children

1,000+ persons per city

CDC/Tufts University

Cohort study

Lowell and Newton, Massachusetts—surface water systems, one with filtered river water and one unfiltered from a partially protected watershed

Children

400 households

EPA

Community intervention trial before and after installation of a filtration plant

Undisclosed city, Massachusetts—surface water system

General population

300 households

EPA

Community intervention trial before and after installation of a filtration plant with ozonation

Seattle, Washington—surface water system

Children and elderly

300 households

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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Exposure Measurements

Health Outcomes

Epidemiologic Measure of Association

Status (as of January 2004)

Consumption of tap water treated with either real or sham device

Gastrointestinal Illness

Attributable fraction

Data collection ongoing

Consumption of tap water. Water quality measured by turbidity and presence of Cryptosporidium oocysts in finished water

Prevalence of Cryptosporidium antibodies in serum and saliva specimens, and episodes of gastrointestinal illness

Correlations of exposures and outcomes over time

Data analysis ongoing

Consumption of tap water and exposure to recreational water. Water quality measured by turbidity and presence of Cryptosporidium oocysts in finished water

Prevalence of Cryptosporidium antibodies in serum and saliva specimens, and episodes of gastrointestinal illness

Relative risk and correlations of exposures and outcomes over time

Data analysis ongoing

ICR data on source water monitoring

Seroprevalence of Cryptosporidium antibodies and episodes of gastrointestinal illness before and after the intervention

Attributable fraction

Study completed, results not published

ICR data on source water monitoring

Seroprevalence of Cryptosporidium antibodies and episodes of gastrointestinal illness before and after the intervention

Attributable fraction

Study completed, AWWARF report (Project #2367) in preparation

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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Study Sponsor/Primary Institution

Study Design

Geographic Location—Water System

Population

Study Size

EPA

Community intervention trial before and after installation of microfiltration

Texas groundwater system under the influence of surface water

General population

200 households

San Francisco Department of Public Health and University of California, San Francisco

Case-control study

San Francisco, California

Persons with AIDS

49 cases and 99 matched controls

In conclusion, a substantial effort to determine the potential health risks associated with the consumption of drinking water has been going on in the United States since the late-1980s, while surveillance for waterborne disease outbreaks has been continuous for several decades. However, most of these efforts have not focused on associating specific waterborne pathogens with indicators, and associating pathogens and their indicators with illness. Linking gastrointestinal illness with water consumption is not the epidemiologic equivalent of linking the illness to waterborne pathogens and indicators despite the intuitive understanding that the two hypotheses are closely related.

Data collection efforts in outbreak investigations of drinking water have concentrated mostly on identifying the epidemiologic link to water consumption and identifying a pathogen in clinical specimens rather than in water samples. When water samples are tested for bacterial indicators such as total and fecal coliforms, the samples that are collected are typically from finished water (especially at the treatment plant and not in the distribution system) rather than source water, in part because only the treated water is ingested. As mentioned previously, in many outbreak investigations the water is no longer contaminated or the indicator/pathogen is present in such low concentrations by the time water samples are collected that the resulting water analyses are negative. It is often difficult to collect water samples quickly enough that the sample is representative of the water quality that was likely responsible for the outbreak. Nevertheless, timely and thorough investigations of drinking water outbreaks can provide epidemiologic data associating poor water quality with adverse health outcomes.

To date, few data exist to correlate indicators with pathogens in drinking

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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Exposure Measurements

Health Outcomes

Epidemiologic Measure of Association

Status (as of January 2004)

ICR data on source water monitoring

Seroprevalence of Cryptosporidium antibodies and episodes of gastrointestinal illness before and after the intervention

Attributable fraction

Data collection ongoing

Tap water consumption inside and outside the home

Development of cryptosporidiosis

Odds ratio Attributable fraction

Results published (Aragon, 2003)

water and with endemic adverse health outcomes in the United States. Although Payment’s study (1991) and Colford’s pilot study (2002) did find an association between drinking water and gastrointestinal illness, the Payment study did not find any correlation between illness and the indicators that were measured and the Colford study was not designed to look at this association. In addition, the Big WET study did not show an association between drinking water and illness and it remains to be seen if any of the secondary analyses when linked to the water quality data collected in the nested study will provide measurable epidemiologic associations. To have adequate statistical power to address the epidemiologic association of health outcomes with specific indicators and waterborne pathogens, the study sample size must be large, and therefore the costs can become prohibitively expensive. Once again, if water quality is monitored, the choice is to test the water that is consumed rather than the water at its source and along its distribution system. Nevertheless, recent studies have begun to include tests for indicators and pathogens in water, and it remains to be seen if the results will show correlations with adverse health outcomes.

Epidemiologic Studies of Diseases Attributed to Recreational Water

As reviewed in Chapter 1, the development of microbial water quality criteria and standards based on health effects assessments from prospective epidemiologic studies did not occur until the 1950s. Of particular importance, Stevenson (1953) reported the results of a series of USPHS studies at three pairs of bathing sites on Lake Michigan, along the Ohio River, and on Long Island Sound. The

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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Stevenson study results indicated that swimmers showed increased rates of illness over non-swimmers per 1,000 person-days of activity, and illness rates tended to rise with increased swimming days. The symptoms reported included eye, ear, nose and throat, as well as gastrointestinal illness. Overall, there was not a consistent correlation found between levels of illness and levels of coliform bacteria measured in bathing water when the data for all study sites were examined. However, specific data from Lake Michigan freshwater beaches suggested increased illness rates at total coliform levels of about 2,300 per 100 mL. This value was subsequently lowered by a factor of approximately two in order to obtain a total coliform indicator standard of 1,000 per 100 ml. Thus, as discussed in Chapter 1, this value of total coliforms became the basis for the subsequent bacteriological water quality criteria recommended by the National Technical Advisory Committee (NTAC) of the FWPCA, after conversion to fecal coliforms concentrations based on the ratio of total to fecal coliforms (NTAC, 1968).

As noted previously, the Stevenson study and the subsequent development of the FWPCA-NTAC recreational water quality criteria derived from it in 1968 were criticized as inadequate in several ways. This criticism ultimately resulted in a National Research Council (NRC, 1972) report, Drinking Water and Health, Volume 1 (see also Appendix B). Notably, the NRC report concluded, “No specific recommendation is made concerning the presence or concentrations of microorganisms in bathing water because of the paucity of valid epidemiological data” (NRC, 1972). The fecal coliform measurement itself was also criticized, with the report noting that thermotolerant bacteria such as Klebsiella spp. read positive in this test but are not necessarily fecal in origin. In addition, the NTAC fecal coliform criteria did not account for the considerable daily variability in water quality; the relatively loose definition of swimming did not require immersion of the head, which would result in greater exposure to water; and beach-going but nonswimming control participants were not included.

Because of the recognized deficiencies of previous studies (see also Chapter 1), EPA conducted prospective epidemiologic-microbiological studies in the 1970s to compare rates of gastrointestinal illness in swimmers and beach-going non-swimmers at fresh and marine beaches differing in microbial water quality and sources of fecal contamination. These studies by Cabelli and colleagues (Cabelli et al., 1982) used more rigorous definitions of gastrointestinal illness and included a number of different microbial indicators of fecal contamination in water, including enterococci and Escherichia coli.

From these studies it was concluded that concentrations of enterococci best correlated with gastrointestinal illness (e.g., vomiting, diarrhea, nausea, stomach ache) attributable to swimming in marine waters and that both enterococci and E. coli best correlated with such illness in fecal contaminated freshwaters. Log-linear relationships between mean enterococcus or E. coli density per 100 mL and swimming-associated rates for gastrointestinal symptoms per 1,000 persons were subsequently developed. These became the basis for current marine and fresh

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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recreational water quality criteria and guidelines that were calculated using geometric mean values of several (generally 5 or more) equally spaced samples over a 30-day period: E. coli not to exceed 126 per 100 mL, or enterococci not to exceed 33 per 100 mL in freshwater; enterococci not to exceed 35 per 100 mL in marine water (Cabelli, 1983; Dufour, 1984; EPA, 1986). Single-sample maximum allowable densities were also promulgated based on beach use. These values were based on risk levels of 8 and 19 gastrointestinal illnesses per 1,000 swimmers at freshwater and marine beaches, respectively, and they were estimated to be equivalent to the risk levels for criteria of 200 fecal coliforms per 100 mL.

These pivotal studies by EPA prompted numerous epidemiologic-microbiological studies of similar and improved design in many parts of the world (see Table 2-3 and systematic review of these and other recreational water studies by Wade et al., 2003). Many of the more recent studies attempted to improve and expand upon these prospective epidemiologic studies by EPA in several respects. For example, some addressed a broader range of swimming-associated health effects such as respiratory illness, while others obtained better estimates of the microbial quality of water to which bathers were actually exposed by more intensive and extensive sampling to address spatial and temporal variability of water quality. Some studies measured concentrations of even more microbial indicators such as coliphages, and others measured concentrations of enteric pathogens such as enteric viruses and parasites.

Throughout the 1980s and 1990s, data from various recreational water quality studies around the world began to emerge. Consistent with its goal to develop a harmonized framework for science-based guidelines on water quality and health, WHO developed a uniform approach to recreational water quality, commonly referred to as the “Annapolis Protocol” (Bartram and Rees, 1999; WHO, 1999). This approach provides a harmonized risk assessment and management framework for recreational water. It was developed in response to the need to establish an effective and harmonized approach to monitoring and managing fecal contamination of recreational waters. Some of the key recommendations in the Annapolis Protocol include the following: (1) moving away from sole reliance on “guideline” values of fecal indicator bacteria toward use of a qualitative ranking of fecal loading in recreational water environments, supported by direct measurement of appropriate fecal indicators and (2) provisions to account for the impact of actions to discourage water use during periods or in areas of higher risk. The protocol has been tested in several countries, and recommendations resulting from these tests have been included in new WHO Guidelines for Safe Recreational Water Environments (see WHO, 2003).

The results of many of the historical and more recent prospective epidemiologic-microbiological studies were compiled and summarized in a review article by Prüss (1998) as part of the WHO effort to develop and harmonize recreational water quality criteria and guidelines (Fewtrell and Bartram, 2001; WHO, 1999).

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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TABLE 2-3 Selected Studies Used for Analysis of Health Effects and Microbial Water Quality Relationships in Recreational Waters

Authors

Year

Country

Study Design

Water

Stevenson a,b,c

1953

United States

Randomized controlled Trial

Fresh

Mujeriego et al. a,d

1982

Spain

Retrospective cohort (cross-sectional study)

Marine

Cabelli et al. a,d

1982

United States

Prospective cohort

Fresh, Marine

Cabelli a,b,d

1983

Egypt

Prospective cohort

Marine

Dufour a,d

1984

United States

Prospective cohort

Fresh

Seyfried et al.

1985

Canada

Prospective cohort

Fresh

Fattal et al., UNEP/WHO no. 20 a,c

1987

Israel

Prospective cohort

Marine

Lightfoot

1989

Canada

Prospective cohort

Fresh

Ferley et al. a,b,d

1989

France

Retrospective cohort

Fresh

Cheung et al. a,d

1989

Hong Kong

Prospective cohort

Marine

UNEP/WHO no. 53 a,c,d

1991

Spain

Prospective cohort

Marine

UNEP/WHO no. 46 a,c

1991

Israel

Prospective cohort

Marine

Fewtrell et al. c,e

1992

United Kingdom

Prospective cohort

Fresh

Corbett et al. c,d

1993

Australia

Prospective cohort

Marine

Pike a,b,d

1994

United Kingdom

Prospective cohort (cross-sectional study)

Marine

Kay et al. c

1994

United Kingdom

Randomized controlled Trial

Marine

Medical Research Councilb,d

1995

South Africa

Prospective cohort

Marine

Kueh et al. a

1995

Hong Kong

Prospective cohort

Marine

Bandaranayake c

1995

New Zealand

Prospective cohort

Marine

Van Dijk et al. b

1996

United Kingdom

Prospective cohort

Marine

Haile et al.

1996

United States

Prospective cohort

Marine

Fleisher et al. c

1996

United Kingdom

Randomized controlled Trial

Marine

aControl for less than three confounders reported, or not reported at all.

bExposure not defined as head immersion, head splashing, or water ingestion.

c<1,700 bathers and 1,700 nonbathers participating in the study.

dOnly use of seasonal mean for analysis of association with outcome reported.

eExposure is white-water canoeing, considered similar to swimming, with intake likely.

SOURCE: Adapted from WHO, 1998.

Of the 37 studies evaluated by Prüss, 22 qualified for inclusion in the evaluation. Figure 2-1 presents the relationship between indicator organism density in marine water and illness risk for bathers. A similar compilation of the results for studies in fresh recreational waters is shown in Figure 2-2. Of the 22 studies selected for analysis, 17 were prospective cohort studies, 2 were retrospective

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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FIGURE 2-1 Relationships of risks of illness in swimmers to the microbial quality of water—marine recreational waters. Note: Solid lines indicate actual data from original studies whereas dashed lines are extrapolations of data by Prüss (1998) or Pike (1991). SOURCE: Reprinted, with permission, from Prüss, 1998 © Oxford University Press.

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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FIGURE 2-2 Relationships of risks of illness in swimmers to the microbial quality of water—fresh recreational waters. Note: Solid lines indicate actual data from original studies whereas dashed lines are extrapolations of data by Prüss (1998) or Pike (1991). SOURCE: Reprinted, with permission, from Prüss, 1998 © Oxford University Press.

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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cohort studies, and 3 were randomized controlled trials, as summarized in Table 2-3. Of the studies examined, the rate of certain symptoms or groups of symptoms was found to be significantly related to the count of fecal indicator bacteria in recreational water. Thus, there was a consistency across the various studies evaluated and gastrointestinal symptoms were the most frequent health outcome for which significant dose-related associations were reported. In marine waters, fecal streptococci or enterococci were the fecal indicators that best predicted gastrointestinal illness. In freshwaters, increased concentrations of fecal coliforms or Escherichia coli as well as fecal streptococci and enterococci were predictive of increased gastrointestinal illness risks. Staphylococci concentrations were also found to be predictive of increased risks of illness, including ear, skin, respiratory, and gastrointestinal illness. Although these latter relationships were attributed to the effects of bather density, this was not actually proven.

Based on the studies evaluated by Prüss (1998), strong and consistent associations have been reported between microbial indicators and various adverse health effects to include temporal and dose-response relationships. Furthermore, these studies have biological plausibility and analogy to clinical cases from drinking contaminated water. However, various biases commonly occur with epidemiologic studies as summarized in Table 2-4.

For marine bathing waters, randomized controlled trials in the United Kingdom (Fleisher et al., 1996; Kay et al., 1994) probably contained the least amount of bias. These studies also provide the most accurate measure of exposure, water quality, and illness compared to observational studies where an artificially low threshold and flattened dose-response curve (due to misclassification bias) were likely to have been determined. Therefore, the United Kingdom randomized controlled trials form the key studies for derivation of guideline values for the microbiological quality of recreational waters.8It should be recognized that these recommended guidelines values are from studies in temperate waters and are not characteristic of the tropical and subtropical waters found in many areas of the United States (e.g., the U.S. Gulf coast).

Based on analyses of data from numerous studies on the relationships between swimming-associated health effects and the microbial quality of bathing water, the WHO and other international as well as national entities have concluded that fecal streptococci and enterococci currently are the fecal indicator microorganisms that best predict health risks in recreational waters (WHO, 2001). Rather than classify recreational waters as either acceptable or unacceptable, WHO experts chose instead to establish a five-tiered classification system (i.e.,

8  

Guideline values are nonregulatory values for constituents in water, in this case microbial indicators, developed by the World Health Organization (see Bartram and Rees, 1999 and WHO, 2003 for further information).

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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TABLE 2-4 Types of Biases Potentially Encountered in Recreational Water Quality Health Effects Studies

Type of Bias

Description

Use of indicator microbes to assess water quality

Temporal and spatial indicator variation is substantial and difficult to relate to individual bathers (Fleisher, 1990) unless study design is experimental (Kay et al., 1994; Fleisher et al., 1996); limited precision of methods for counting indicator organisms, causing measurement error (Fleisher, 1990; Fleisher et al., 1993); bacterial indicators may not be representative of viruses, which may be important etiological agents

Use of seasonal means to assess water quality

Some studies use seasonal means and not daily measurements of indicator organisms to characterize individual exposure, thus adding substantial inaccuracy

Assessment of exposure pathway

Certain studies do not account for the potential infection pathway to definite exposure (e.g., mainly head immersion or ingestion of water for gastrointestinal symptoms).

Difficulties in exposure recall further increase inaccuracy of individual exposure

Non-control for confounders

Non-control for confounders (e.g., food and drink intake, age, sex, history of certain diseases, drug use, personal contact, additional bathing, sun, socioeconomic factors) may influence the observed association

Selection of unrepresentative study population

Results reported for certain study populations (e.g., limited age groups regions with certain endemicities) are a priori not directly transferable to populations with other characteristics

Self-reporting of symptoms

Most observational studies relied on self-reporting of symptoms by study populations. Validation of symptoms by medical examination (Fleisher et al., 1996; Kay et al., 1994) would reduce potential bias. External factors, such as media or publicity, may have influenced self-reporting

Response rate

Response rates were >70% in all, and >80% in most studies. Differential reporting (e.g., higher response among participants experiencing symptoms) would probably not have major consequences

Recruitment method

Recruitment methods were to approach persons on beaches in almost all observational studies and by advertisement for randomized controlled studies

Interviewer effect

Differences in methodology of data collection among interviewers may influence study results

 

SOURCES: Adapted from Prüss, 1998; Stavros and Langford, 2002; WHO, 2001.

very poor, poor, fair, good, or very good) based on microbial water quality (using fecal streptococci or enterococci indicator counts) and sanitary condition (based on sanitary inspection or survey) to identify likely health risks (WHO, 2001, 2003).

It is important to note that few studies used to establish the WHO recre-

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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ational microbial water quality classification system based on fecal streptococci or enterococci included a wide range of candidate fecal indicator microbes or pathogens. Therefore, it must not be assumed that fecal streptococci or enterococci are the only or even the most predictive fecal indicators of health risks from recreational water quality exposures.

Other candidate indicators that have not been adequately studied or for which reliable methods were previously not available may eventually prove to be more predictive and reliable fecal indicators of human health risks than are fecal streptococci or enterococci.

Systematic Review of Recreational Water Studies

At the request of this committee, Colford (2002) and colleagues (Wade et al., 2003) were asked to conduct a meta-analysis or similar synthesis of the various epidemiologic-microbiologic health effects studies available in the world’s literature. After establishing study characteristic and quality criteria, they identified a total of 27 (17 marine water and 10 freshwater) studies for a “systematic review”9 including 24 cohort studies, 2 randomized trials, and 1 case-control study. From these studies, a subset was found to be amenable to the determination of relative risk of a health outcome, such as gastrointestinal, respiratory, skin, ear, or eye effects.

For gastrointestinal illness, several indicators showed significant associations with the levels of the following indicators in recreational water: fecal streptococci (enterococci), fecal coliforms, E. coli, total coliforms (marine water only), enteroviruses (marine water only), and coliphages (freshwater only) in water. When regression analysis was used to examine the log relative risk of illness against indicator level in water, positive associations were found for fecal streptococci (enterococci). The authors concluded that E. coli and enterococci were the “best” indicators of gastrointestinal illness in marine water, while there was no best (consistent) indicator of gastrointestinal illness in freshwater. A log (base 10) unit increase in enterococci was associated with a 1.34 (range 1.00-1.75) increase in relative risk in marine waters and a log (base 10) unit increase in E. coli was associated with a 2.12 (range 0.93-4.85) increase in relative risk in freshwater. It was also noted that enteroviruses and bacteriophages may be promising indicators to predict risk of gastrointestinal illness, but there are too few studies to

9  

A systematic review involves a predefined rigorous review of existing studies, may or may not include meta-analyses, and can be exemplified by the Cochrane Review (http://www.cochrane.org). Rothman and Greenland (1998) define meta-analysis as a “statistical analysis of a collection of studies, especially an analysis in which studies are the primary unit of analysis. Meta-analysis methods thus focus on contrasting and combining results from different studies, in the hopes of identifying consistent patterns and sources of disagreement among those results.”

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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establish their utility at this time. Overall, the study results supported the use of enterococci in marine waters at EPA levels.

None of the commonly used microbial indicators consistently predicted risks of respiratory illness, but relative risks of skin disorders tended to increase with several indicators, including fecal streptococci (enterococci), fecal coliforms, and E. coli. The results of these studies provide encouraging evidence that predictive associations exist or can be found between various swimming-associated health effects and various microbial indicators or pathogens in recreational bathing waters. However, Wade and colleagues identified several major research gaps that need to be addressed regarding the use of indicators for recreational waters, including the following:

  1. studies of immunocompromised populations;

  2. studies in other sensitive/vulnerable subpopulations such as children and the elderly;

  3. determination of etiologies by analysis of clinical specimens;

  4. additional rigorously conducted epidemiologic studies such as observational studies that have standardized definitions of exposure and health outcomes and standardized methods, as well as randomized trials to establish etiology;

  5. additional studies using enteric viruses and bacteriophages as water quality indicators;

  6. use of combinations of water quality indicators to assess overall health risks; and

  7. analysis of the effects of study location and climate on results.

The results of the systematic review of recreational water epidemiologic studies by Wade and colleagues (2003) provided several informative observations and led to some important conclusions from the authors, which are supported by the committee: (1) the analysis documented that a more thorough meta-analysis of many of the international studies on recreational water quality and health effects is both possible and able to provide useful data to further interpretation and related decision making; (2) it pointed out both study design and data weaknesses and gaps that can be filled in future epidemiologic-microbiological studies of recreational water quality and health; (3) it indicated that bacterial indicators such as enterococci, E. coli, and fecal streptococci could provide reliable estimates of water quality that are predictive of human health risks under some, but not all, water quality conditions (e.g., statistically, enterococci followed by E. coli were the best indicators in marine waters, but there were insufficient data to make similar conclusions about freshwaters); and (4) it also provided evidence that other microbial fecal indicators, such as coliphages and certain pathogens were predictive of human health risks, despite the fact that few studies included these water quality tests. Therefore, these other microbial indicators deserve further consideration in future studies.

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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EPA’s BEACH Act Studies

As part of EPA’s Action Plan for Beaches and Recreational Waters and legislative assistance from the Beaches Environmental Assessment and Coastal Health (BEACH) Act of 2000 (see also Chapter 1), EPA is conducting annual national survey(s) on state and local microbial water quality monitoring efforts, and will begin collecting health effects data (EPA, 1999). CDC is collaborating with EPA on the health effects studies, which use a prospective cohort design. Several Great Lakes and marine sites will be evaluated, including one that served first as the pilot site. Health outcomes to be studied include both enteric and nonenteric (e.g., respiratory illnesses, dermatitis, eye and ear infections) disease. The pilot study was conducted at one freshwater recreational beach (Indiana Dunes National Lakeshore) during the summer of 2002 to evaluate public response rates, to test the questionnaire, and to establish the study’s operational protocols. Two beaches were studied during the summer of 2003, one in Indiana and one in Ohio. Enrollment criteria included all persons on the beach regardless of gender and age. Biological specimens were not collected. However, EPA still hopes to collect these specimens, including stool, serum, and saliva in some subset of the study population.

Sites will include both freshwater and marine beaches but not tropical or subtropical recreational waters. Indicators that might be used include enterococci and E. coli but not total and fecal coliforms. Other potential microbial and chemical indicators are still being considered but will focus solely on human sources of fecal contamination. Although nonpoint sources of contamination (e.g., fecal contamination from nonhuman sources, runoff, rainfall) will not be addressed due to lack of funding, they should be included in future epidemiologic studies of recreational water exposure (see also Chapter 4). In addition, habitual users of recreational water, such as professional surfers, will not be studied despite the fact that knowledge is lacking on the epidemiology of chronic or recurrent illness in these populations (e.g., eye and ear infections). EPA’s goal is to have a water quality test that will provide results within two hours so that a determination can be made to close the beach if deemed necessary prior to the time visitors are expected to begin arriving (Alfred Dufour, EPA, personal communication, 2002).

QUANTITATIVE MICROBIAL RISK ASSESSMENT

Historically, as noted throughout this report, acceptable microbial levels for evidence of pathogen risk in drinking water, contact recreational waters, and shellfish harvesting waters have been set using indicator organisms, most often the coliform (either total or fecal) group. The recognition of many of the pathogens responsible for waterborne disease from microbiological and epidemiologic investigations, the advent of better methods for direct measurement of pathogens in water (Gerba and Rose, 1990; Gregory, 1994; Leong, 1983; Ongerth, 1989; Rose,

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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FIGURE 2-3 Schematic of ILSI microbial risk assessment protocol. SOURCE: Adapted from ILSI, 1996.

1990; Rose et al., 1991a,b; Sobsey, 1999, 2001), and the development of risk assessment paradigms for developing risk management systems and setting environmental standards (NRC, 1983, 1989; Silbergeld, 1993) provide a basis for the application of quantitative microbial risk assessment to the development of risk criteria for establishing microbial standards of acceptable water quality. These analytic advances provide a rational basis for either validating, revising, refuting, supplementing, or replacing traditional microbial indicator measurements.

The quantitative microbiological risk assessment approach follows the framework proposed for (chemical) risk assessment in the seminal 1983 NRC report Risk Assessment in the Federal Government: Managing the Process, which includes the following basic steps: hazard assessment, exposure assessment, dose-response analysis, risk characterization, and risk management. Alternative but similar protocols have been published—for example, by the International Life Sciences Institute (ILSI, 1996, 2000)—that are specifically designed to apply to waterborne pathogens. A schematic of the ILSI protocol is shown in Figure 2-3. Notably, this protocol more clearly emphasizes the interrelationships between the technical and policy-making components surrounding the risk assessment process, particularly at the problem formulation stage.

Several substantive differences exist, however, between the assessment of risk from microorganisms and the assessment of risk from chemicals, including the following:

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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  • Exposure to microorganisms from water generally involves the ingestion of low numbers (up to tens or hundreds) of microorganisms. Exposure to chemical agents even at very low doses involves quite larger numbers (thousands or much greater numbers) of molecules.10 At low numbers (as with microorganisms), there may be large differences between individuals with respect to the actual number of organisms ingested induced by pure statistical sampling variability, while with large numbers (as with chemical agents), this source of variability is quite small with respect to other sources. Thus, the assessment of exposure, and dose-response with microorganisms must consider this intrinsic sampling and exposure variability, while chemical risk assessment can ignore this phenomenon.

  • For microorganisms, there is strong biological information to indicate that as few as one microorganism has the potential to cause harm (Haas et al., 1999b). That is, there is a non-zero probability that one organism can initiate infection. For chemical agents, it may be (depending on the agent and the mode of action) that far more units (molecules) are necessary to provoke an effect. In the case of microbial agents, it is generally the case11 that an ingested microorganism has the potential to multiply within the body and thereby produce sufficient microorganisms in vivo to result in illness. This does not mean that ingesting a single organism in and of itself will always produce illness since an organism may be killed by defense processes (e.g., the acidity of the gastrointestinal tract, the immune system) prior to reproducing in sufficient amounts to have an adverse effect. However, one organism potentially (if it and a sufficient number of its progeny survive) has the biological potential to produce an effect.

  • Individuals’ microbial exposure may have subsequent impact on the broader population (including individuals that do not ingest pathogenic microorganisms from water). Once infected (even if not symptomatic), an individual may infect others and cause others to become ill through person-to-person contact and other transmission routes unrelated to water. This is called secondary spread, and the degree of such spread depends on the organism (its infectivity, excretion pattern, and intensity and duration of contagion) and the behavioral aspects of infected individuals.12 Often the extent and magnitude of such effects are difficult

10  

Consider the exposure to 1 ng (10−9 g) of a chemical with a molecular weight of 100. This is the exposure to 10−11 moles of substance. Since there are 6.02 × 1023 molecules in a mole (Avogadro’s number), this amounts to an exposure to 6 × 1012 molecules (6 trillion molecules).

11  

The exception being microorganisms that produce toxins as they grow in the environment, such as algae, and where the ingested toxins, rather than the ingested cells themselves, result in an adverse effect. However, as noted in Chapter 1, blue-green algae and their toxins are specifically excluded from the study charge.

12  

For example, infected adults are believed to have better hygienic practices, such as handwashing, compared to children, and therefore infected adults may produce fewer secondary cases than children. In addition, the number of susceptible persons with whom an infected person may come in contact is an important factor.

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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to assess, however they may represent an important element of public health risk estimates. Another potential population factor is that prior exposure to a particular microorganism (via water or other routes) may induce partial or complete immunity in an individual. That is, the individual may become less susceptible (partial immunity) or completely resistant (complete immunity) to subsequent exposures. This immunity may be of permanent or temporary duration. In the case of Cryptosporidium, rechallenges of individuals with oocysts a year after prior exposure has been found to confer partial immunity (i.e., a shift in the dose-response curve) to an additional exposure (Chappell et al., 1999). Whether such immunity persists for a longer duration and whether a similar effect is operative with other pathogens are not well established. However, this type of information would help make a quantitative microbial risk assessment more accurate, and such data can be used in more comprehensive, dynamic, risk assessments (Eisenberg et al., 1996, 1998).

It should be noted that quantitative microbial risk assessment, like risk assessment in general, has many inputs that are uncertain. These include uncertainty about the best dose-response model for the pathogen or indicator organism of interest and its behavior in the low dose region, assumptions about water consumption and other water-related exposures, and uncertainty about occurrence and concentration of pathogens or indicators in water. In addition, there may be variable host susceptibility and immunity to infection, etc. (some of which may be clarified with increasing knowledge of genetic determinants of host susceptibility to certain microbial pathogens). However, such limitations to current knowledge should not prohibit QMRA from being conducted, but rather (as with all risk assessments), it must be recognized that such analyses need to be updated as the state of knowledge evolves.

Case Studies

Since the advent of QMRA in the 1980s, there have been a number of articles published showing the application of this method for recreational waters (e.g., Haas, 1983a; 1986) and drinking water; two case studies for drinking water exposure are described below.

Risk from Ingestion of Giardia in Drinking Water

Using data from human volunteer studies, Regli et al. (1991) developed a dose-response relationship for infection from ingestion of Giardia lamblia that was compared to attack rates observed in waterborne outbreaks (Rose et al., 1991b) to assess the likelihood that an infected person would become ill. Researchers used a target risk of 1 infection in 10,000 persons per year—which was regarded as acceptable by EPA in the Surface Water Treatment Rule (SWTR; see also

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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Chapter 1)—and a daily average water consumption of 2 liters per person per day to estimate that an acceptable finished water concentration would be 6.75 × 10−6 per liter (i.e., one organism in 148,000 liters). Since verification of such a low level of microbial occurrence constitutes a technological impossibility, a graphical relationship between the microbial quality of source water and the number of logs of reduction required to reduce the microbial level to the acceptable value was developed.

In the initial SWTR a tiered treatment requirement was proposed that would incorporate this approach. However, in the final promulgated regulation a single fixed value of log reduction (3 log10, 99.9 percent) was required, based on an estimated upper value of source water microbial levels across the United States (EPA, 1989). In addition, because this approach did not adequately address other contaminants such as viruses and Cryptosporidium, the ICR (see Table 1-1), which was promulgated later (EPA, 1996), focused on source water monitoring for pathogens.

New York City: Cryptosporidium

The current New York City water system uses chlorination alone and has been exempted from filtration under a Memorandum of Agreement signed on January 21, 1997, between New York City, New York State, EPA, and other regional and environmental organizations. An intensive watershed protection and monitoring program has been mandated to ensure the water quality of its Catskill and Delaware ambient surface water supplies. A previous NRC committee performed a study on the effectiveness of this program in ensuring water quality in the future (NRC, 2000; see also Appendix B). As part of this study, monitoring data for Cryptosporidium parvum were used to conduct a risk assessment for consumers of water from the Catskill and Delaware systems. A dose-response relationship developed from human feeding studies was employed (Haas et al., 1996). Based on consideration of the variability and uncertainty of the inputs, it was concluded that the estimated risk to consumers from Cryptosporidium parvum infection was in excess of 1/10,000 per year, and thus—if this level was to be regarded as “acceptable”—additional reduction of oocyst levels would be necessary.

Acceptance by International Organizations

In the field of water quality, WHO has recently developed an overall framework for guideline and standard setting in all of its water-related activities—including drinking water, recreational water, and exposure to effluents and sludges from the agricultural use of such materials—using microbial risk assessment as a foundation (Fewtrell and Bartram, 2001). Specifically, the framework suggests that while risk assessment is a central element of water quality guideline

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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and standard development, particular guidelines may be framed in terms of indicators (rather than pathogens) and the entire process is in need of continual refinement based on environmental monitoring data and public health surveillance (see Figure 2-4; Bartram et al., 2001).

Outside the water field, microbial risk assessment has increasingly been adopted both in the United States and internationally as a paradigm for developing standards for food safety. It is outside the scope of this report to review the field of food risk assessment; however, several recent studies describe and review such developments (e.g., Buchanan and Whiting, 1996; Hoornstra and Notermans, 2001; Jaykus, 1996; Ranta and Maijala, 2002).

Data Requirements

One of the key needs for QMRA is dose-response information. In the initial applications of this technique, reliance was placed on human dose-response information. For example, studies were done in the 1950s on human response to

FIGURE 2-4 Conceptual framework for development of water-related microbial standards.

SOURCE: Adapted from Bartram et al., 2001.

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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ingestion of Salmonella and other enteric bacterial pathogens (June et al., 1953; McCullough and Eisele, 1951a,b,c,d); somewhat later, human trials on response to viral ingestion were performed (Minor et al., 1981; Ward et al., 1986). Human volunteer trials of exposure to Cryptosporidium have been reported and are still being conducted (Chappell et al., 1996; Dupont et al., 1995; Okhuysen et al., 1998, 1999; Teunis et al., 1997, 2002a,b). However, it is increasingly less likely, owing to ethical and logistical concerns, that human volunteer data could be used to develop such information in the future. Therefore, alternative sources of such information must be developed.

In particular, the use of alternative sources of data will be important to understand the role and magnitude of human and microorganism variability in influencing the risk. From human feeding trials with Cryptosporidium, these factors appear highly significant (Teunis et al., 2002a,b); however, the use of different methods to obtain such information will be required with other microorganisms.

One alternative approach may be the increased use of animal models. These have been found useful in understanding the dose-response relationship of Listeria monocytogenes and Escherichia coli O157:H7 (Haas et al., 1999a, 2000). In general, the use of animal models is considered appropriate if the mechanisms and pathways for the processes of infection and disease are likely to be the same in experimental animals and humans and there are some waterborne pathogens for which this is the case. For example, Havellar et al. (2001) developed and evaluated a rat experimental model to study dose-response relationships of the enteropathogenic bacterium Salmonella enterica serovar Enteritidis. The authors concluded that the rat model is a sensitive and reproducible tool for studying the effects of oral exposure to Salmonella Enteritidis over a wide dose range and allows controlled quantification of different factors related to the host, pathogen, and food matrix in initial stages of infection by these bacterial pathogens. That study demonstrated that animal model systems of human infection and disease have advantages over human studies, such as the ability to examine the events leading to infection and disease at the cell, tissues, and organ level, including pathophysiological mechanisms and pathways. It also demonstrated the ability to score for mortality as an end point. The validation of animal models requires, in addition to a competent animal species, data from human outbreak studies in which attack rates and exposure are reliably estimated. For risk assessment, it is therefore particularly important in the use of epidemiologic outbreak data that greater effort be devoted to dose reconstruction. It should be noted that demonstrating that a particular animal is a competent species is a complex task, and therefore for newly emerging (or recognized) pathogens such development may require a significant research effort.

A second approach would be to use information obtained directly from the epidemiologic study of an outbreak to develop a dose-response relationship. For example, a drinking water outbreak of Giardia showed a graded response between attack rate and self-reported glasses of water consumed (Istre et al., 1984).

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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This was subsequently analyzed using an exponential dose-response relationship (between attack rate and glasses of water) (Rose et al., 1991b). However, the unavailability of a measurement of concentration of the pathogens at the time of exposure prevented the full development of a dose-response relationship.

A third approach to obtaining alternative sources of data is to examine in a risk assessment context historical dose-response data for enteric pathogens that have been given to humans. For example, numerous studies were done in which human volunteers, both adults and children, were challenged with different doses of hepatitis A virus and scored for infection and illness (Ward et al., 1958). These data have yet to be examined using QMRA techniques. Although the doses administered to the volunteers were not measured directly, they can be estimated on the basis of the expected concentrations of pathogens in the sample (e.g., an acute phase serum), based on more recent analytical information of measurements of hepatitis A virus in sera, and a distribution of the concentration can be put into dose-response models.

Relationship of QMRA to Microbial Indicators

The application of indicators or direct pathogen monitoring provides data that can be used within the QMRA framework to set criteria for establishing water quality standards and define the potential public health risk. Each approach, described below, has its own merits, difficulties, and uncertainties.

Direct Pathogen Monitoring

For any particular pathogen, QMRA may be used to develop a risk-related criterion. However, such criteria have to be considered carefully based on the methodology used to measure the particular pathogens in the water environment. Measurements can be based on infectivity or culturability, viability, physical presence (as detected by microscopy), or detection of microbial components (nucleic acids, proteins, or specific antigens; see Chapter 5 and Appendix C for further information). Estimations and interpretations of risk must consider how well these different measurement techniques detect infectious microorganisms that pose human health risks. However, as described earlier, the concentration of a pathogen in water at the point of exposure that would be allowed as an “acceptable risk” is likely to be much lower than can be practically and reliably detected, as with finished drinking water (Regli et al., 1991; Rose et al., 1991a,b). Thus, alternative approaches toward implementing risk-derived guidelines may be necessary. One approach would be to include key pathogen monitoring requirements in National Pollutant Discharge Elimination System (NPDES; see Table 1-2) permits where the discharge may be affecting key designated bodies of water. Historically, pathogen requirements have rarely been included in wastewater discharge permits (NRC, 2000). The formal computation of a risk assessment based

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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on pathogen monitoring data also would enable those interested in designing novel sensor and analysis approaches to understand the required level of sensitivity of such systems if they are to be used in controlling risk from exposure to waterborne pathogens.

Indicators and Dose-Response Relationships

As discussed previously, the basic philosophy behind the EPA recreational water quality criteria is to develop human dose-response relationships between a measured indicator and a measured health effect (presumably due to pathogens in the water) of interest via direct epidemiologic investigation (Cabelli, 1983; Dufour, 1984; Seyfried et al., 1985a,b). From these investigations, the direct health risk from exposure to microbially contaminated recreational water can be determined as a function of a dose metric in terms of indicator concentrations in the water. This approach effectively condenses the dose-response and exposure assessment steps of risk assessment into a single functional relationship, by assuming that the exposure (i.e., amount of water ingested) is the same in epidemiologic investigations and in situations where risk is desired to be controlled.

Indicator-to-Pathogen Ratio

As discussed throughout this chapter, there is considerable evidence that the risk of becoming infected and ill from ingesting waterborne pathogens increases as the numbers or dose of pathogens increases (i.e., a dose-response relationship). Furthermore, it is generally but not always the case that the greater the number of indicator organisms in water and other media, the greater the number of pathogens (see also Chapter 1). In some cases, these indicator-to-pathogen relationships are sufficiently robust that they have been published in peer-reviewed journals, such as the relationship between enteroviruses and F+ coliphage indicators in ambient freshwaters in the Netherlands (Havelaar et al., 2003). While these relationships between indicator organisms and pathogens can change due to variable pathogen or indicator concentration in fecal sources and ambient waters, they do exist at any point in time. One approach to microbial water quality assessment, conceptualized many years ago by Fuhs (1975), would be to develop a thorough analytical monitoring program and a systematic quantitative relationship between pathogen concentrations and indicator concentrations. A more recent and rigorous explication on this concept has shown that indicator to pathogen ratios can then be used to modify the usual dose-response relationships such that the risk of exposure can be determined based on indicator concentrations (Lopez-Pila and Szewzyk, 2000). This approach has application to point sources of pollution discharged to water bodies and to the development of pathogen-to-indicator ratios in sewage and stormwater, combined sewer overflows, and so on. Modeling the impact at the site of exposure (e.g., the beach) would require de-

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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tailed knowledge such as flow and microbial quality about the sources of the pathogens as well as the incorporation of various decay processes (perhaps as influenced by temperature, turbidity, and sunlight) that affect the indicators and the pathogens during transport. Assessing other factors including dilution and accumulation in sediments may also be necessary.

Future Directions for QMRA

To date, most applications of QMRA have focused on the prediction of primary infections or illnesses resulting from exposure to a contaminated medium (water, food, etc.). However, it is clear that for at least some illnesses, significant impact results from secondary transmission (Kappus et al., 1982; Mac Kenzie et al., 1994; Morens et al., 1979). In recent years, mathematical models have been increasingly applied to understanding of disease transmission process—including the processes of secondary transmission and immunity (Eisenberg et al., 1996, 1998). However, such approaches require a variety of data that are not readily available, including intensity and duration of contagion, duration and strength of immunity, and so on. The increased use of such dynamic mathematical frameworks in a sensitivity analysis to help determine the potentially most influential parameters for which there are data gaps, and to use such knowledge in focused epidemiologic investigations to fill these gaps, appears to have merit. The models must be used to inform data gathering, as well as be informed by data. To fully understand long-term and endemic risks associated with certain waterborne illnesses, it will also be necessary to develop models that account for pathogen dynamics in nonhuman reservoirs and survival in water bodies. Feedback between modelers and experimentalists will also be needed to develop data necessary for better quantitative understanding of microbial risk.

SUMMARY: CONCLUSIONS AND RECOMMENDATIONS

Health effects assessments for waterborne pathogens can be based on a number of approaches. Each approach has strengths and weaknesses, and all have been or are being used to document and quantify the health risks of microbes in water.

Epidemiologic methods are a well-established and essential tool for determining linkage between the presence of identified waterborne pathogens and their indicators and human disease. However, the significant cost and methodological difficulty of designing, conducting, and interpreting such studies have limited their use.

The comprehensiveness of investigations of waterborne disease outbreak in the United States varies by the type of outbreak and by state, and results are compiled in CDC’s surveillance system. However, this system has low sensitivity and does not consistently provide information that links indicator and patho-

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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gen data with adverse health outcomes. This gap occurs because most outbreak investigations include primarily the epidemiologic component, which concentrates on linking illness to water and might include determination of the agent in clinical specimens, but tends to neglect the environmental component, which would include the determination of water quality through measurement of indicator and pathogen occurrence in water. This gap occurs more frequently with outbreaks associated with drinking water than with those associated with recreational water. In addition, 40-50 percent of identified outbreaks are of unknown etiology.

Under the SDWA Amendments of 1996, recently completed (though largely unpublished at the time this report was finalized) epidemiologic studies of drinking water and endemic disease have focused on establishing associations between water consumption and gastrointestinal illness. Thus far, they have not established a good correlation between indicators of waterborne pathogens, the pathogens themselves, and adverse human health effects, although some earlier studies have shown an association between tap water and endemic gastrointestinal illness with attributable fractions ranging between 14-40 percent. To have adequate statistical power to address the epidemiologic association of health outcomes with specific indicators and specific waterborne pathogens, the study sample needs to be large, leading to significant costs. In addition, methodologic complexities as well as difficulty in interpretation of results have limited the use of some of the studies.

In contrast, epidemiologic studies involving recreational bathing waters have shown predictive associations between several swimming-associated health effects and various microbial indicators or pathogens. A systematic review and meta-analysis of recreational waterborne studies (both freshwater and marine) confirmed that indicators can provide reliable estimates of water quality that are predictive of human health risks under some, but not all, water quality conditions, and the committee supports several conclusions provided in that study as related to this report.

Under the BEACH Act, the recently initiated EPA study of midwestern and eastern freshwater beaches is commendable, but limited in scope to the study of point-source contamination and acute disease; it does not yet include western regions or ocean beaches. Knowledge is lacking about the epidemiology of chronic or recurrent illness (i.e., gastrointestinal, respiratory, dermatologic illnesses) associated with habitual users of recreational waters subject to point and nonpoint source microbial contamination, and knowledge of the epidemiology of disease outbreaks associated with use of tropical and subtropical recreational waters and ocean beaches is fragmentary.

Quantitative microbiological risk assessment follows the traditional framework proposed for chemical risk assessment with several substantive differences. QMRA is a useful tool for identifying data gaps, especially models that include infectious disease parameters such as immunity. However, some of the key needs for QMRA are dose-response and exposure information (e.g., intensity and dura-

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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tion of contagion), which are often lacking. In some cases, impacts from such population level phenomena may dramatically alter projected estimates of human risk.

Building on its conclusions, the committee makes several recommendations regarding future directions for epidemiologic and microbiological research as related to health effects assessment of waterborne pathogens and their indicators. The committee first recommends that EPA and CDC take a greater leadership role in such efforts, and fund and work with stakeholders and academic researchers in the following areas:

  • CDC should actively work with state and local health departments to encourage testing for pathogens (especially viruses and parasites) in clinical specimens during waterborne outbreak investigations.

  • Standardized laboratory methods for clinical specimens as well as water samples which are both sensitive and specific must be developed for many viruses.

  • CDC and EPA should actively work with state and local health departments to encourage collection and testing of environmental data (i.e., water quality data for source, finished, and distribution system waters that include indicators and pathogens) during waterborne outbreak investigations.

  • Standardized protocols and definitions are needed for outbreak investigations and epidemiologic studies, especially to help ensure a comprehensive investigation or study that includes the collection of clinical, laboratory, and environmental data (including co-occurrence of pathogens and indicators).

  • Epidemiologic studies should be conducted to (1) assess the effectiveness and validity of newly developed indicators or indicator approaches for determining poor microbial water quality and (2) assess the effectiveness of the indicators or indicator approaches at preventing and reducing human disease.

  • Fewer but more comprehensive epidemiologic studies should be conducted rather than multiple small-scale studies that do not adequately address multiple risk factors and health outcomes when working within a fixed or constrained budget. More specifically, the link between pathogens and their potential indicators, and among pathogens, indicators, and adverse health outcomes, would be strengthened by including in comprehensive and adequately funded studies, epidemiologic measurements of health outcomes, measurements of pathogens in clinical specimens, as well as measurements of pathogens and their potential indicators in relevant water samples.

  • Additional epidemiologic studies are needed to look at the association between water consumption and gastrointestinal illness in groundwater systems, and to correlate water quality data (pathogens and indicators) with health outcomes. Furthermore, these studies should include the collection of epidemiologic, clinical, laboratory, and environmental data whenever feasible.

  • Health outcomes studied in association with drinking water exposure

Suggested Citation:"2 Health Effects Assessment." National Research Council. 2004. Indicators for Waterborne Pathogens. Washington, DC: The National Academies Press. doi: 10.17226/11010.
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should not be limited to gastrointestinal illness (e.g., should consider respiratory and dermatological illnesses).

  • The national estimate of waterborne disease should be expanded. Specifically, data have to be incorporated from sources other than randomized intervention trials and community trials (e.g., outbreaks, systematic reviews and meta-analyses, Cryptosporidium serologic data from NHANES, data from models derived from risk assessment).

  • Additional epidemiologic studies should be conducted to determine the occurrence of chronic/recurrent disease attributable to waterborne pathogens in habitual users of recreational waters (e.g., surfers) from point and nonpoint sources of contamination.

  • Studies of recreational waters should be carried out on a broader range of geographical and ecological sites, including tropical and subtropical waters and ocean beaches.

  • Indicators being studied as part of the BEACH Act should not be limited to those than can yield results in two hours, as has been suggested.

  • Since epidemiologic investigations are mandated as part of the BEACH Act, consistent scientific approaches should be used to monitor for various types of indicators as well as pathogens to establish dose-response relationships.

  • Alternative sources to human volunteer data should be pursued to provide dose-response and exposure information for QMRA.

  • Risk assessment with sensitivity analyses should be used to identify data gaps and help drive epidemiologic studies.

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Recent and forecasted advances in microbiology, molecular biology, and analytical chemistry have made it timely to reassess the current paradigm of relying predominantly or exclusively on traditional bacterial indicators for all types of waterborne pathogens.Β Nonetheless, indicator approaches will still be required for the foreseeable future because it is not practical or feasible to monitor for the complete spectrum of microorganisms that may occur in water, and many known pathogens are difficult to detect directly and reliably in water samples.Β

This comprehensive report recommends the development and use of a β€œtool box” approach by the U.S Environmental Protection Agency and others for assessing microbial water quality in which available indicator organisms (and/or pathogens in some cases) and detection method(s) are matched to the requirements of a particular application.Β The report further recommends the use of a phased, three-level monitoring framework to support the selection of indicators and indicator approaches.Β

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