United States
Environmental Protection Office of Water EPA 815-R-98-004
Agency 4607 August 1998
Waterborne Disease Workshoo
October 9 and 10/1997
Meeting Summary
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Environmental Protection Agency
WATERBORNE DISEASE WORKSHOP
' October 9 and 10, 1997
Washington National Airport Hilton
Arlington, Virginia
MEETING SUMMARY
Final
July 20, 1998
Prepared by RESOLVE
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Final WBD Workshop - Oct 9-10, 1997
Meeting Summary
CONTENTS
INTRODUCTION l
I BACKGROUND OF WATERBORNE DISEASE DETECTION AND FEDERAL
POLICY DEVELOPMENT 1
I. l STATUTORY REQUIREMENTS AND DIRECTION OF MICROBIAL DRINKJNG WATER REGULATIONS
AND EPA/CDC PARTNERSHIP.... 1
1.2 PASSIVE SURVEILLANCE, TRANSMISSION, AND SEROLOGICAL TESTING 3
1.3 DEVELOPrNG NATIONAL WATERBORNE DISEASE ESTIMATES FOR DRINKING WATER
REGULATIONS 4
/. 3.1 Influence of national waterborne disease estimate on regulations : 4
1.4 DETECTION OF WATERBORNE DISEASE (ENDEMIC AND EPIDEMIC) AND INHERENT
DIFFICULTIES AND LIMITATIONS 5
1.4.1 Current System Strengths 5
1.4.2 Current System Weaknesses 6
1.4.3 Alternative Surveillance Approaches 6
1.5 INITIAL INVESTIGATIONS: INCLUDING S-CITY STUDY AND CDC's EMERGING INFECTIONS
PROGRAM SITES :,.-. 8
1.5.1 Attributable Fraction -(Proportion of total illness due to drinking water.) 8
1.5.2 Design Issues 9
1.6 INCIDENCE OF GASTROINTESTINAL ILLNESS - CROSS SECTIONAL STUDIES 10
II PLANNED AND ONGOING STUDIES OF DISEASE OCCURRENCE 12
II. I A R,\Ni>oMi/.r.o. TRIPLE-BUNDED. PLACEBO-CONTROLLED TRIAL OF THE FEASIBILITY OF
HOUSEHOLD DRINKING WATER INTERVENTION STUDIES 12
//././ Advantages 13
II. 1.2 Disadvantages 13
II. 1.3 Ethical issues ..' 13
II. 1.4 Discussion 13
H.2 COMMUNITY ENTERIC STUDY-- STUDY DESIGN MODEL 15
11.2.1 11.2.1 Discussion Points ." 16
11.3 A PAIRED CITY STUDY-- STUDY DESIGN MODEI ; 16
//. j. / Discussion Points ." 77
11.4 RANDOMI/ED COMMUNITY TRIAL -- STUDY DESIGN MODEI 17
11.4.1 Method -. 17
11.4.2 Discussion 19
11.5 TIME SERIES -- STUDY DESIGN MODEL '. 20
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III APPROACHES TOWARDS A NATIONAL ESTIMATE ~ 22
HI. l CAUSATIVE FACTORS & SITE SELECTION 22
llll.I General : 22
III. 1.2 Source Water (Surface/Ground) , 22
HI. 1.3 Treatment Method/Technology 22
111. 1.4 Reportability and Compliance 22
III. 1.5 Site Selection 23
HI. 1.6 Choice of System and System Size 23
111.1.7 Number and Types of Sites Needed for Portfolio 24
III. 1.8 Indicators of Exposure to Pathogens and Disease 24
III. 1.9 Distribution Systems '. 25
III. 1.10 Specific Pathogens 25
HI. 1.11 Immuno-Compromised Sub-Populations 25
III.2 SOCIETAL IMPACT ,25
111.2.1 Health Issues 25
III. 2.2 Economic Issues ; 26
HI. 2.3 Equity/Justice Issues '. 26
111.3 MP.TIIODS ." 26
III.3.I General : 2(5
111.3.2 Case Control -. 26
III.3.3 Prospective Cohort 27
III.3.4 'Household Intervention :.. 27
111.3.5 Community Intervention 27
IH.4 STUDY SCALE- TOR NATIONAL CSTIMATJI 27
III. 4.1 Scientific and Policy Credibility' "' 28
III.5 NUXTSTEPS! u '. 28
ill.6 AMERICAN WATER WORKS ASSOCIATION RESEARCH FOUNDATION 28
III.7 ADDITIONAL SITE SELECTION CONSIDERATIONS AND CLOSING REMARKS 28
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Meeting Summary
Attachments
Presentation Notes
A. Stig Regli Presentation Notes: Statutory Requirements
B. Jeffrey Griffiths Handout: Routes of Exposure / Spread and Detection of Waterborne
Infectious Disease
C: Dennis Juranek Presentation Notes:
1. National Estimate of Waterborne Disease Occurrence
2. Ongoinc CDC Surveillance Systems Related to Water 1996
3. Incidence of Gastrointestinal Illness
D. Jack Colford Presentation Notes: Toward a National Estimate of Waterborne
Diseases: A Randomized. Triple-Blinded. Placebo-Controlled Trial of the Feasibility
of Household Drinking Water Intervention Studies
i
C. Rebecca L. Calderon Presentation Notes: Community Enteric Studv: Enteric Disease
Study
Phase I site selection
Phase II site evaluation
Phase III pilot (full scale) ~
!'. Floyd Frost Presentation Notes: Survey Results from Paired City Study
Meeting Information
(i. Agenda
H. Participant List
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Introduction
The Environmental Protection Agency (EPA) and Centers for Disease Control and
Prevention (CDC), as recommended by the M/DBP Expedited Rule Advisory Committee
resolution, co-sponsored the Waterborne Disease Workshop on October 9 and 10, 1997.
The objectives of the Workshop were to:
Provide background on the Safe Drinking Water Act mandate to conduct waterborne
disease occurrence studies and develop a national estimate of waterborne disease
incidence;
Discuss how these studies fit into the larger public policy framework on providing
safe drinking water;
Discuss planned and ongoing epidemiological studies and Environmental Protection
Agency & Centers for Disease Control activities related to these mandates;
Identify data gaps, research needs, and opportunities for improved methodologies,
and:
Discuss next steps and opportunities for coordination and communication.
This report summarizes the presentations and discussion at the Workshop. It is organized
in three sections; The (I.) Background ofAVaterbornc Disease Detection and Federal
Policy Development section includes summaries of the presentations by Agency
representatives concerning the scientific and policy considerations in developing a
National Estimate for Waterborne Disease Occurrence. The (II.) Planned and Ongoing
Studies of Disease Occurrence section summarizes presentations on specific ongoing or
proposed research approaches and the discussion surrounding them. The (HI.)
Approaches Towards a National Estimatc'section summarizes the discussion of
scientific and policy considerations involved in developing the National Estimate. The
presentation of the discussions throughout this summary are grouped by topic and not
necessarily sequential.
I Background Of Waterborne Disease Detection And Federal Policy
Development
l.l Statutory requirements and direction of microbial drinking water regulations
and EPA/CDC partnership1
-Presented by Stig Regli, EPA
Regli provided the regulatory background for the objectives of the Workshop, and EPA's
regulatory mandate. The EPA. Regli explained, must set a maximum contaminant level
goal (MCLG) for contaminants of concern. By regulation, this MCLG must be "set at a
level where no known or anticipated health effects occur and which allows an adequate
margin of safety." MCLG's for Giardia and viruses are set at zero and the EPA has
formally proposed setting an MCLG of zero for Crypiosporidium. The MCLG is not an
' See attached for Stig Regli presentation notes: Attachment A.
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Meeting Summary
enforceable standard but rather a benchmark used for setting the regulatory standard.
EPA must set a Maximum Containment Level (MCL) or treatment technique
requirements (TTR) as close to the MCLG as feasible taking costs into consideration. If
the MCL or the TTR would result in an increase in risk due to other contaminants in the
drinking water, EPA can set the MCL or the TTR at a level that minimizes the overall
risk by balancing the risks" from the different contaminants instead of setting the standard
at the "feasible" level.
Regli continued that the costs associated with reducing the risks posed by waterbome
disease are considered to be in the range of $100 millions to billions per year, so it is
important to find a way to quantify the benefits associated with taking action. The
magnitude of the risk created by taking action due to other contaminants in the drinking
water (such as risks from disinfection byproducts) must be also considered. Regli
pointed out that there are large uncertainties associated with quantifying each of these
risks.
Responding to a question from a Workshop participant. Regli explained that EPA's
current approach to regulating drinking water does not include direct measurement of
pathogens. In the Surface Water Treatment Rule (SWTR) EPA required a fixed level of
treatment for Giardia and viruses. The level of treatment was thought to be adequate for
most supplies. This assumption was based-en a limited amount of source water Giurdia
occurrence data. The cost and the difficulties of pathogen monitoring at the time made it
infcasible to require systems to monitor their source water and to set a treatment standard
based on site specific source water pathogen levels. (It is possible that future regulations
will require monitoring of source water in order to establish the appropriate level of
treatment.) Regli continued to explain the basis for selection of a target organism for
developing the TTR. By requiring treatment to provide a certain reduction in the
concentration of the target organism(s), the drinking water concentration of other less
treatment resistant microbes will be reduced to acceptable levels. In the case of the
SWTR, the target organisms were Giurdia'and Hepatitis A virus. The efficacy of the
treatment to reduce the concentrations of the target organisms is based on laboratory
bench and pilot scale studies. It is not currently feasible to base regulations on the
detection of microorganisms in finished water because of the high frequency of large-
volume of finished water samples that would be required to ensure high probabilities of
safety and detection sensitivity (I [or less than 1] in 10.000 liters which is below
currently viable technology). Indirect approaches are being considered based on
prescribing appropriate levels of treatment.
EPA has redirected $1 million of the S10 million health effects research budget for FY 07
towards the CDC studies on waterborne disease occurrence. Additional funds for this
purpose are expected in FY 98. EPA and CDC have not decided on a research design for
the next step in this process.. Regli. as well as other EPA and CDC representatives.
assured the participants that no decisions on what studies will be commissioned have
been made and that the discussions at this meeting would be used to review present
approaches, gather alternatives, and inform future decisions. This Workshop and the
upcoming AWWARF January 1998 meeting will provide input on the types of studies
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Meeting Summary
that could provide information necessary for developing the national estimate and which
may be useful in developing the future microbial regulations.
1.2 Passive Surveillance, Transmission, and Serological Testing
-Presented by Dr. Jeffrey Griffiths, Tufts University2
Introductory remarks, and presentation of an interpretation of passive surveillance,
transmission, and serological testing by Dr. Jeffrey Griffiths, Tufts University,
representing the National Association of People with AIDS.
Dr.. Griffiths gave a very brief overview describing some of the reasons why this
workshop was being held. He related that members of the FACA committee (committee
established under the Federal Advisory Committee Act to provide advice to EPA on the
development of the Interim Enhanced Surface Water Treatment Ruleand Stage 1 of the
Disinfectant / Disinfectant Byproduct Rule) had expressed frustration about the limits of
knowledge about water borne cryptosporidiosis. and water borne diseases in general. The
FACA committee had unanimously voted to ask the EPA and CDC to hold this
workshop, in order to review currently funded studies on waterbome diseases, and to
strategize on future studies, in the presence of an outside panel of experts in water borne
diseases. He presented two flow charts describing the Routes of Exposure to WBD and
Spread and Infection with Waterhorne Infectious Diseases. These charts were
accompanied by a review of the serological literature. Three points were made by
Griffiths in ihese charts and the review.
I. The first is that detection of clinical cryptosporidiosis is a rare event, even in the
setting of ongoing endemic widespread exposure, and that traditional passive
surveillance is likely to miss more than 99.9% of the disease. [Dr. Dennis Juranek of
the CDC reinforced this point in his discussion; indeed, only 12 of 250,0000 people
with clinical cryptosporidiosis during the Milwaukee outbreak were detected by
passive surveillance (4.8 per 100.000) during the largest known waterborne disease
outbreak in the history of the United States |. (See the first chart)
2. Secondly, the issues of exposure, infection, secondary spread, and eventual detection
of the disease are complex and in Griffiths' opinion, cannot be easily modeled by the
equation, total GI illness x attributable fraction due to water = a national estimate of
waterborne diseases. Primary reasons for this skepticism include the need to account
for secondary transmission, and person-to-person spread after waterborne
introduction into a community. The second chart details these transmission cycles.
3. Thirdly, extensive documentation from the literature was provided that the published
seroprevalence data is likely to be an underestimate of lifetime exposure rates.
perhaps by as much as two orders of magnitude, and that the duration of a serological
response to parasite qocysts is short (months, not years).
: See attached for Jeffrey Griffiths handout: Attachment B.
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1.3 Developing national water borne disease estimates for drinking water
regulations3
-Presented by Stig Regli, EPA
The second part of Regli's presentation described how the Agency has traditionally
estimated the national level of infectious disease associated with drinking water in its
regulatory impact analysis. The Agency's approach to develop this national estimate is
to:
Select target organisms (i.e., Cryptosporidium, Giardia, and viruses).
Estimate national distribution of the target pathogen concentration levels reaching
consumers. [This is done by assessing the distribution of target pathogen
concentrations in the source waters nationwide and then applying a treatment
reduction factor to estimate the distribution of target pathogens in the drinking water
at the tap.]
Estimate infection rates from an available dose response curve, [e.g. by extrapolation
from the dose response curve for Cryptosporidium a person has a 0.5% likelihood of
infection due to ingestion of a single oocyst.J
Estimate (based on the above data) national illness and mortality rates.
'*
Regli continued with a discussion of the uncertainties and issues limiting the estimate of
infectious disease associated with drinking water using the methodology outlined above.
Difficulty of measuring the source water pathogen concentration levels.
Source water occurrence is highly variable (many samples needed per site to get a
reliable estimate.)
Available pathogen analytical methods have poor recovery rates (i.e. they arc
imprecise, and have high detection limits., they cannot yet measure viability or
infectivity of pathogens).
Difficulty in obtaining reliable treatment estimates (filtration and disinfection
performance)
Lack of data on the health effects of infection by specific pathogens:
Dose response curves vary by organism strain and host-derived factors including
levels of immunity in the exposed individual (putting aside at this point the effect
of herd immunity which affects secondary transmission.)
Symptomatic response of humans is not well defined.
/. 3.1 Influence of national \vaterhorne disease estimate on regulations
Regli discussed how the results of epidemiological studies that will be conducted to
develop the national estimate could help define the stringency of additional microbial
treatment regulations. To the extent that these studies identify the etiologic agent causing
infectious disease associated with drinking water, they will help define the level of
treatment necessary, i.e. there are significant differences in the effectiveness of
disinfectants to inactivate different microbes, as well as differences in the effectiveness of
physical removal. If studies determine that disease is associated with bacteria in the
See attached for Regli presentation slides: Attachment A.
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Meeting Summary
distribution system, then this may support limits on bacterial growth or enhanced cross
connection control. However, Ron Hoffer, EPA, explained that the congressional
mandate does not specifically link national estimate to any specific regulatory action.
Regli continued that the Agency hopes that the national estimate will inform the
discussion on the level of stringency for future regulations and on the risk factors
associated with waterborne disease. This may lead to higher and/or more consistent
levels of treatment for pathogens in source waters (especially for protozoa or viruses) and
improvements in distribution system controls (such as limiting bacteria growth and
contamination intrusions into piping.)
Regli clarified that the goal of the workshop was to hear from those persons who were
involved in conducting epidemiology studies for EPA and CDC, and to listen to the
comments and ideas of others with expertise or an interest in this area of research. Sue
Binder, CDC, later in the meeting added that through this review and joint-deliberation
the Agencies hope to improve current studies, augment understanding of waterborne
disease occurrence, and expand on the idea of a portfolio of relevant research. Binder
concluded that .this Workshop should help EPA and CDC clarify what is missing from the
current body of studies and identify next steps.
1.4 Detection of Waterborne Discase^endcmic and epidemic) and inherent
difficulties and limitations4
-Presented by Dennis Juranek, CCfC
Jurnnek's overview of the current waterborne disease surveillance system included the
CDC's objectives, an explanation of how the system works, a discussion of the sensitivity
and limitations of the system, and cxamples'of the performance of the system during
outbreaks. The current system does not provide data suitable for estimating the National
prevalence of waterborne disease. Juranek explained that there are many obstacles to the
detection and reporting of waterborne disease outbreaks. He used the example of a
Milwaukee 1993 waterborne disease outbreak. In a questionnaire survey 250.000 people
were found to have had onset on watery diarrhea before local health officials were aware
of a waterborne outbreak. Only 12 made it through the many obstacles that prevent cases
from being recognized and reported to the local health department. Most illnesses (94%)
were not recognized by-the medical community because people did not seek medical
assistance. Of those who sought medical care, only 6% were tested for parasites, and
only 4% of those were tested for Cryptosporidium (12 tested positive). Thus only 1 in
24.000 cases sought and received medical care/laboratory services that resulted in their
illness being reported. According to one participant, the system may not detect outbreaks
of diarrhea unless more than 1% of the population gets infected. For a more complete
discussion of these topics please refer to the materials that Juranek used in his
presentation (attached Appendix C).
/. -/. / Current System Strengths
Juranek pointed out that the advantages of the current surveillance system are mainly a
result of health departments' experience in using the system and CDC's ability to
4 See attached for summary of presentation: Dennis Juranek. Attachment C.2.
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Meeting Summary
summarize and publish data in timely fashion. The current system also provides a
historical frame of reference for data and is relatively inexpensive to maintain when
compared with other types of data collection systems.
1.4.2 Current System Weaknesses
Juranek also pointed out that the current system has many weaknesses that should be
taken into account when quoting or interpreting the data. The system is passive
(voluntary) and may miss many small-scale outbreaks. The system has trouble detecting
outbreaks if physicians do not report cases to health departments or to CDC. The system
is further compromised by the fact that persons with gastrointestinal illness frequently do
not seek health care. In some instances physicians do not pursue the cause of illness by
ordering the appropriate laboratory tests. Thus the causes of mild and moderate illnesses
are often undetermined or misdiagnosed. Laboratories may not routinely test stool for
pathogens transmitted by water, especially new ones like Cryptosporidium or
Cyclospora. Heath Maintenance Organization (HMO) emphasis on cost reduction may
further decrease requests for laboratory tests for specific pathogens in the future. There
arc also lengthy delays between onset of an outbreak and its detection, investigation, and
reporting. This not only reduces the opportunity to take immediate corrective action to
reduce the number of people who are exposed, but also reduces the chances for
identifying the etiologic agent or the water treatment failure that lead to the outbreak.
y ~
1.4.3 Alternative Surveillance Approaches
Juranek then outlined some of the approaches that were suggested at a 1994 workshop at
CDC to improve surveillance for Cryptosporidium outbreaks. The group then discussed
each alternative.
1.) Make Crvntosnoridium outbreaks reportable legally to CDC. This approach provides
a baseline against which increased numbers during an outbreak may be compared.
However, it does not improve diagnosis or reporting by physicians or increase routine
lab testing. One participant pointed out that this approach is more likely to reflect
infections in immunocompromised people or children than in the general public.
2.) Monitor laboratory diagnoses (tests for Crvptnsnoridiiim in stool or scrum
antibodies.) Five states are currently undertaking active review of laboratory records
to detect cases. One participant discussed New York City's laboratory monitoring
efforts. New York City looks actively for Giardia and Cryptosporidium. According
to this participant, N.Y. public health experts felt that before they started monitoring
laboratories they were missing half the diagnosed cases of Cryptosporidium infection.
In Connecticut 4-5 times more cases of Cryptosporidium were detected through
active lab monitoring than were reported before monitoring. These cases were
identified by laboratorians. but labs-were failing to report all of them to the health
department. Other participants pointed out that the problems with this approach are
the expense of monitoring and the unreliability of monitoring for the amount of
disease in the community. It was also pointed out that it is illegal for laboratories to
charge for tests that are not specifically ordered by the patient or physician. Some
participants pointed out, however, that blind active surveillance of fecal samples was
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Meeting Summary
both possible and legal, so long as no charge is made for an unordered test. A
number of participants volunteered that they have conducted or are conducting such
studies.
It was pointed out b.y some members of the panel, that the phrase "active review" of
laboratory records was in their opinion simply improving the yield of passive
surveillance, and was not a substitute for true active surveillance in the estimation of
cryptosporidiosis. Furthermore, these panelists pointed out that even with a doubling
of the rate of passively reported cases of cryptosporidiosis, this would only alter the
number of cases missed by passive surveillance from 99.95% to about 99.90%.
3.) Monitor sales of anti-diarrheal medication (indicator of infection). Juranek explained
that this approach captures some of the population that does not seek further medical
attention. It does not, according to one participant, distinguish between the many
routes of exposure including water (drinking and recreational exposure such as
swimming), food, person to person spread, or animal contact. It would, however.
indicate increased incidence and permit more rapid and focused investitiation.
4.) Monitor HMO and hospital lous (indicator of diarrhea). Juranek pointed out that this
approach is particularly useful if medical facilities have computerized systems for
logging telephone calls regarding patient illnesses. Information entered promptly into
a computerized database can effectiveHy monitor both complaints of diarrhea and
severity of gastrointestinal disease in a community. One participant explained that
this approach has additional power because it captures data on all medical complaints
for the total population served. This can be used as a denominator tor calculating an
overall infection or disease rate.
5.) Monitor nursing homes for health effects associated with, infection. According to one
participant "this is a topic so complicated that it needs its own two day conference."
The increased immunity of the elderly to many pathogens (because of repeated
exposure to pathogens over a lifetime) was mentioned by one participant as an
argument against focusing research on this population.
6.) Combine disease and water quality surveillance information for a more complete
picture of the correlation between the two. Juranek mentioned that CDC and EPA
will be sharing information in an effort to correlate changes in water quality with
waterborne disease occurrence. Other participants agreed that this approach had the
added benefit of connecting disease with water quality and pathogen source data.
One participant noted that studies linking water quality and clinical gastroenteritis are
already being published (e.g. Morris et al 1996, Schwartz at al 1997).
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1.5 Initial Investigations: including 5-city study and CDC's Emerging Infections
Program Sites3
-Presented by Dennis Juranek, CDC
Juranek continued the discussion by outlining the CDC and EPA activities toward
developing the Congressionally mandated National Estimate of Waterborne Disease
Occurrence. This presentation included a description of the March 1997 workshop at
CDC, as well as a brief description of CDC's Emerging Infection Program and FoodNet
Program that are monitoring the occurrences of diseases in seven sites nationally.
Juranek clarified the important questions that CDC and EPA would like to answer as part
of any major effort to develop a national risk estimate.
What populations are at greatest risk?
What is the social and economic impact of waterborne disease ?
Which infectious agents cause waterborne disease? And what is their relative
contribution?
What are the characteristics of water systems that are more likely to lead to
waterborne disease?
.£*.
Juranek indicated that one approach to developing a national risk estimate was to
determine how much gastrointestinal illrress was occurring in the country (Total illness)
and multiply that number by the percent of illness believed to be waterborne (Attributable
traction). (See formula below).
(Total cases of GI illness x Attributable fraction due to water) = National Estimate
It was pointed out by CDC personnel that the use of the Emerging Infections and
FoodNet Programs might provide an inexpensive or rapid way to obtain an estimate for .
total cases of GI illness. However, a number of the panelists felt this approach was
potentially Hawed because those sites were not chosen for reasons relating to water
supplies. Representatives of the water industry pointed out that a variety of sites that
reflected different types of water sources would be a more rational choice. Some
members of the panel felt the formula outlined above was too simplistic an approach.
/. 5.1 Attributable Fraction -(Proportion of total illness due to drinking water.)
Participants agreed that this fraction, important for deriving the national estimate, is the
most difficult to measure with precision. One participant suggested that it might be
incorrect to assume that you can easily identify the specific proportion of waterborne
illness that is related only to drinking the water. For example, it may be impossible to
distinguish the initial outbreak cases who actually drank the contaminated water from
those cases acquired by secondary spread from person-to-person, from food, or from
other routes of infection. It was.pointed out that after the Milwaukee outbreak, many
secondary cases were identified that were linked to exposure to swimming pools
See attached for summary of presentation: Juranek. Attachment C.I.
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Meeting Summary
contaminated by children who had initially acquired infection from drinking Milwaukee
tap water.
Several study designs were suggested by Juranek and discussed by the group for
obtaining data on the "Attributable Fraction" of illness due to drinking water. These are
outlined below. Discussions included a review of strengths and weaknesses of each study
design. (For a more complete discussion of this topic please see Juranek's presentation
notes, Appendix C.I.)-
1) Case - Control (e.g. based on doctor or clinic reported cases): trying to identify
the source (s) of exposures for cases by comparing their answers to questions with
those of non-ill persons (controls) seen by the same doctor or at the same clinic.
One caveat is that they may constitute a cohort with an increased proportion of
immune subjects (from prior exposure).
2) Cohort (e.g. HMO based study): follow a study group of people for a year or
more to see who becomes ill and then try to determine through use of a
questionnaire what ill people did differently than people who remained well
during the observation period.
3) Community Intervention (before & after comparison): use of "natural experiment"
situations such as when a utility changes its treatment method. Investigators then.
measure changes in the occurrence o£illness in the community, i.e., after a city
builds and begins to operate a commvinity water filtration plant, is the illness rate
in the community lower than it was before filtration was used.
4) Household Intervention (controlled trial): randomly assign one group of
households drinking water made as microbe-free as possible while a control group
of households in the same area receives the same quality of drinking water as they
normally would from their tap.
Juranek also reviewed some of the major types of .study bias, confounding, and sample
si/e issues that arc inherent in some of the study designs.
1.5.2 Design Issues .
(. 'use ascertainment bias (or who gets included in the study group.) - Case
ascertainment bias is most likely to have a negative impact on Case-Control and
Cohort studies. Participants discussed the difficulties of choosing cases in a ''case-
control" study that are representative of the entire population. According to some
participants, severe cases of illness are more likely to be detected and counted. This
includes persons with .immuno-compromising illnesses and children. People who do
not have easy access to health care or who have different health care seeking
behaviors are unlikely to be counted. Other sources of bias mentioned by participants
were the differences between populations in behaviors that affect risk such as
consumption of tap versus bottled water and uncertainty that the distribution of risks
for infection is the same for comparable groups in different cities.
Confounding Variables (Confounding is a distortion in the association between an
exposure variable and a outcome variable due to some other variable.) - Confounding
is most likely to have a negative impact on Case-Control and Cohort studies. Many
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Meeting Summary
participants brought up the difficulties in trying to eliminate confounding. For
example bottled water users may appear to be at lower risk for gastrointestinal illness
than tap water drinkers, but the lower risk may be a false impression, i.e. it is possible
that bottled water drinkers as a group are more health conscious about everything
they do. Thus they may have lower illness rates because in addition to drinking
bottled water, they also tend to wash their hands well, avoid the types of fast foods
that are often implicated in food-bome outbreaks, etc. Their income level and access
to health care may differ from the general population. Confounding is not a problem
in study designs, such as a household intervention study, where participants are
randomly placed in one of the study groups.
Sample size (or the number of participants needed to show that differences in illness
rates are not due to chance alone). In addition, the number of people in the study
needs to be large enough so that a negative study is meaningful. Participants
discussed the sample size needed from both a technical and political perspective.
According to Juranek, if we believe that drinking tap water caused no more than 1%
of gastrointestinal illness, we would need to study over 50,000 people to prove it.
The need for such large sample sizes reduces the feasibility (i.e. cost and logistics) of
successfully completing a study. Based on "best guesses" and limited published data.
the current estimate of the attributable fraction of mild gastrointestinal illness
associated with drinking tap water may b£ in the 10% to 30% range (Use this
estimated range to calculate the population sizes needed to implement the various
types of study designs described above).'- Based on this analysis, the household
intervention study design was identified as the design that would enable investigators
to test the lowest level of attributable traction with the smallest number of
participants (sample size). Some participants had doubts about the utility of a
household intervention study in enabling a national estimate of waterborne disease to
be generated.
During the course of the Workshop Juranek, as well as Regli and Susan Binder of CDC.
yave overviews of approaches to the National Estimate. Discussion continued throughout
the Workshop on how the Agencies should answer these questions. These discussions
are broken down into specific decision points and are summarized in the Approaches
Towards a National Estimate section of this report.
1.6 Incidence of Gastrointestinal Illness - Cross Sectional Studies''
-Presented by Thomas Navin. CDC
The final portion of Navin's presentation was an overview of the use of cross-sectional
studies to determine the incidence of gastro-intestinal illness. Navin reviewed sources of
baseline data on gastrointestinal illness, emerging infection detection programs in the US.
and the use of FoodNet surveys (part of the Emerging Infections Program). Navin
concluded by mentioning studies of HIV populations and concerns with this, and other.
immuno-suppressed sub-populations.
'' See attached for summary of presentation: Juranek. Attachment C.3.
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The discussion of this presentation concerned the role of immune-compromised sub-
populations in the national estimate and the types of health outcomes (infection with
specific pathogens versus general gastrointestinal illness) that should be the focus of
these studies. The discussion points are included in the Approaches Towards a
National Estimate section of this report.
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II Planned And Ongoing Studies Of Disease Occurrence
II. 1 A Randomized, Triple-Blinded, Placebo-Controlled Trial of the Feasibility of
Household Drinking Water Intervention Studies7
-Presented by Jack Colford, University of California, Berkeley
Jack Colford presented a proposed study design to test the effectiveness of blinding in
household drinking water intervention studies. Health data would also be collected and
the study continued in years 2 and 3 if the study design is found to be appropriate.
Colford began with an overview of the characteristics of the study's design and purpose:
(For a more complete discussion please see Colford presentation notes in Appendix 2.D.).
Randomized & placebo-controlled: Participants are randomly assigned to receive
either water treated at home by special devices or usual water passing through a sham
device.
Triple blinded: Knowledge of the group (active device vs. sham device) to which a
participant is assigned will not be known by the participant, the investigators, or the
statistical team. The households are to be divided into two groups:
''Intervention" groups - households using the devices to treat drinking water.
"Placebo" groups - households using jnactivated devices that resemble active devices
in every visible external characteristic
Duration: 4 to 6 months in the'first year, ideally the study would continue for 12
months for each participant in years 2 and 3.
Devices and Arms of the Study: (choice between point of entry or point of use device
has not been made). The researchers are still contemplating different points of entry
of the device into the homes:
Arm 1 A: Point of entry (to home) device including joint use of filter and
ultraviolet (UV) light enclosed in a locked cabinet that cannot be opened by the
homeowner (tamper seal). .
versus .
Arm I B: Placebo device resembling the point of entry device in all visible
respects except that no filter will be present, the UV source will be disabled and
the .entire device will be encased in a locked cabinet that cannot be opened by the
homeowner (tamper seal).
Arm 2A: Point of entry device including the joint use of filter and UV light on
two faucets in a household (tamper seal).
versus
Arm 2B: Placebo device resembling the point of use device on every faucet in the
household enclosed in cabinet that cannot be opened by participant (tamper seal).
Outcomes to be measured are divided between year 1 and years 2 and 3. Year I
focuses on the effectiveness of the study design including; costs (of conducting a
fullscale study), laboratory outcomes (occurrence of infection with specific
pathogens), and effectiveness of recruitment strategies and retention. Researchers
7 See attached for summary of presentation: Colford, Attachment D.
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will use estimates of health and lab-confirmed outcomes obtained during year 1 to
generate appropriate sample sizes for the studies in years 2 and 3. Years 2 and 3
expand the study with respect to the number of communities and households per
community.
After Colford's description Workshop participants discussed the advantages and
disadvantages of the study design and some of the ethical issues raised by the study
design.
//././ Advantages
Randomized, placebo-controlled design widely used in clinical and experimental
sciences to address controversial questions. The question "does drinking tap water
increase risk of measurable human disease?" is politically controversial because
studies concerning it are likely to attract public, political, and media attention.
Randomization provides the strongest control for "confounding" factors.
In FDA evaluations of drugs, multiple randomized trials are mandated before a new
drug is made available to the public. This study subjects drinking water to this level
of scrutiny.
Results of a (properly conducted) randomized, controlled trial are considered the most
defensible evidence in both scientific arid legal terms.
11.1.2 Disadvantages
Higircost.
Labor intensive.
Requires much more time to conduct than other studies because of the need to recruit
participants and obtain permission from (multiple) institutional review boards (human
subjects committees). .
Only provides data from one site during one particular time period, and therefore will
not be generalizable in the effort to provide a national estimate of waterbornc disease.
Docs not control for waterbornc exposures outside the home.
II. 1.3 Ethical issues
Do investigators have "equipoise"? (a state of scientific uncertainty about the answer
to a research question, or the relationship between outcome and factors tested that
precludes certainty in making a widespread recommendation.)
Is it ethical for corporate or municipal entities to claim that home drinking water is
either healthy or unhealthy in the face of conflicting evidence from uncontrolled, non-
randomized studies?
If the issue under consideration is of widespread public health importance, is it ethical
to omit the most scientifically defensible design from the suite of designs put forth to
address the question?
If. 1.4 Discussion
Following his presentation Colford addressed questions and comments from other
Workshop participants. He indicated that the pilot first year study was not designed to be
large enough to detect small health effect differences between two groups. This study is
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Meeting Summary
most useful as a pilot to gauge the effectiveness of this type of study (in particular the
ability to blinding and if blinding is necessary), but health outcomes will be measured in
the first year as well. Colford suggested that the study should be helpful in deciding if it
is worthwhile doing more blinded intervention studies in future and help clarify what
types of studies should be included in the National Estimate "portfolio".
In response to a question Colford explained that the study will use telephone interviews
coupled with laboratory measurements to determine the incidence of diarrhea but that his
team is looking into other ways of gathering data. This is especially important in the case
of people with underlying medical conditions. Colford responded to a question on the
ethical obligation of researchers to report illness and that if specific infections are .
detected through the laboratory testing, patients will be notified and advised to contact
their personal health care providers. Colford added, however, that there should not be
further ethical issues in administering the filter and sham devices. All the water will meet
current regulations. Some of it will then be treated further. What degree of extra
treatment is still undecided. Water will not be degraded.
One difficulty pointed out by a few Workshop participants is finding a device that would
not change chlorine and taste. A dose of UV will change the quality of the water (i.e.
raise ozone and change taste). One participant recommended that "taste testing" he
conducted because it is likely that participants will taste if their water was treated with
UV light. Even in sham devises there is a, likelihood of changing the drinking water
quality. Additional questions raised on this topic were: how researchers will ensure that
the water coming out of devices is cleaner than tap water? To what extent the device
' further treats the water? And, how will the study account for elevated risk if the device
or sham is not properly maintained?
One participant suggested that this study design only focused on household tap water and
that integrated studies are necessary in the same community while this study is going on.
To accomplish this the ongoing FoodNet survey could be intensified in that area.
Participants pointed out that tying FoodNet survey system to these studies severely
limited the sites where linked studies could be done, and pointed out that the choice of
sites for studies of watcrborne diseases should be made on the basis of the water supply.
not the presence of a FoodNet survey system.
Selection of families with children and the elderly was another issue discussed. The
elderly population could be viewed as immuno-compromised (although they may also
have high resistance to some pathogens). Studying the elderly has the design advantage
that they take most of their water at home.
The topic of timing and prioritizatibn of research was also considered. One Workshop
participant criticized this design because although the study design might be fine from an.
epidcmiological standpoint, the results will not be available for another year. This
question concerned the amount of data that the study would collect. This participant
suggested that the effort should be on low cost studies using retrospective data. Another
comment was that retrospective studies could usefully be.complementary or additional.
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Meeting Summary
rather than an alternative approach. Another question presented was whether the present
focus should be on studies that give indications of incidence of disease.
In response to concerns about the study design one Workshop participant noted that
participants at the March 1997 workshop had favored the household intervention study
design (like the one presented by Colford). Data collected would include signs and
symptoms of gastrointestinal illness, water consumption, collection of clinical specimens
(including stool, sera, saliva), and monitoring of water quality indicators.
At the end of Colford's presentation, Workshop participants made some additional
comments on the proposed household intervention study design;
The device itself, if not maintained, may add to risk - not reduce it - because it
provides more surface area for bacteria to grow.
Most people drink most of their water away from home. A participant asked; how
can you identify and then capture in the study people who only drink water from the
home without then selecting a group who are elderly or immuno-compromised.
liomebound people.
There is a.need to look into doing these studies in multiple sites because differences
between sites might be more important than other confounding factors.
It would also be a good idea to investigate using a less expensive design because k
could be used at more sites. ?
In the discussion of the household intervention design one participant suggested an
alternative approach based on a "community" intervention with randomization by
community (not individual household). A presentation and discussion of this study design
was added to the next day's agenda.
11.2 Community Enteric Study8Study Design Model
-Presented by Rebecca Caldcron, EPA
Rebecca Calderon presented CPA's efforts to study rates of enteric disease using a
longitudinal study - following 300 families with children between 2 and 10. The study
integrates surveillance (clinical lab results, HMO/nurse hotlines, and cross sectional
survey) and indirect measures of illness (nursing home surveillance, hospital admissions,
antidiarrheal sales, and school absenteeism) to compare with symptom reporting in the
families. Researchers could use utilities that are currently planning on making changes in
their water source, treatment, or distribution systems (either in response to EPA
regulations or not) and use them as opportunities to do "natural" before/after
experiments. (For a more complete discussion please see Calderon presentation notes in
Appendix 2.D.). .
Calderon presented the four objectives of the study;
Determine the enteric disease rates in various communities across the country.
Determine the relative source contribution of environmental factors associated with
enteric disease.
" See attached for summary of presentation: Calderon,. Attachment E.
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Meeting Summary
Determine etiologic agents associated with enteric disease.
Evaluate methods of surveillance.
//. 2.1 Discussion Points
Calderon explained that this effort began with site identification, looking for communities
that would be useful because they were changing their water treatment systems - a
natural time series experiment. This task was harder than expected and she spent two
years identifying unfiltered utilities changing to filtered treatment systems. Many of the
unfiltered plants were not aware that EPA regulations required them to install filtration.
Calderon has currently identified 5 plants that are upgrading to filtered water treatment
systems. Calderon also found that many other plants are changing - i.e. groundwater to
surface water, treatment technology, etc. One participant commented that this is great
opportunity to do comparative before/after epidemiology studies.
Dr. Calderon explained that in her experience gaining trust in a community is the hardest
part of doing a community-based study. Especially concerning the collection of blood.
Calderon had done sero-surveys previously with success in other communities. In those
communities the Red Cross helped in collecting blood samples. In this study the Red
Cross was not used and citizens were reluctant to give blood samples. The solution was
to lost local college students. They were happy to give blood for money ($25), they also-
returned so they could be monitored ovef time. For the serum testing Calderon chose a
college with mostly local students so they were not traveling as much as students from
other regions during breaks. Students would have to remain in an area through different
seasons, because of the variability of water quality during different seasons. Participants
noted difficulties with using Red Cross sera, as they do not represent the population as a
whole, and voiced the same concerns about college students. Other specific populations
of interest identified included children and parents of young children.
According to Calderon. one of the current challenges to understanding WBD occurrence
is the lack of surveillance. Calderon suggested that if studies were continued over time
researchers could gain experience and have a much better idea of what is going on. .An
advantage of this study design is that it is an integrated approach that could easily
become part of a surveillance .system.
11.3 A Paired City Study -- Study Design Model')
-Presented by Floyd Frost, Lovelace Institute
Floyd Frost presented his work on a completed "paired city" study comparing Las Vegas
and Albuquerque. The study looks at infections among residents of both cities. The
study used infection as an endpoint "because a very small percentage of infections result in
illness (estimated 1/100 to I /1000) and even fewer cases of illness result in a report to
CDC (estimated 1/100,000 to I/million). The study investigated serum response to
Cryptosporidium in individuals and used a benchmark of 35% to represent a "serum-
positive". This number was chosen because few baselines were above this number. The
" See attached for results from paired city survey: Frost. Attachment F.
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Meeting Summary
duration of serum response (IgG - up to one year) makes it possible to identify recent
infections with high rates of confidence. Two years after an outbreak in Las Vegas (LV),
Nevada, responses for two Cryptosporidium-specific antigen groups were evaluated for
200 LV and 200 Albuquerque. New Mexico blood donors to determine if endemic
Cryptosporidium infection was elevated in LV. LV participants had higher mean
responses to the 15/17 kDa marker. However, for late September-early October. 1996.
Albuquerque participants had higher mean responses for both markers, corresponding to
an increase in the point prevalence of cryptosporidiosis cases in New Mexico and several
other states. More LV participants used bottled water or had a home water filter system,
but these precautions were not associated with lower serological response to either
marker. Washing food with bottled water was associated with an increased response for
the 15/17 kDa marker. These results suggest that the contribution of LV drinking water
to infection during this time might be modest.
II. 3.1 Discussion Points
The discussion following Dr. Frost's presentation centered on the confounders that could
complicate the drawing of conclusions from data collected in an epidemiological study.
Eating vegetables has been shown to have protective effect for illness. However, is this
because of curative/preventative vegetables or increased exposure/immunity?
''*
. A study in an area of Ecuador where water - because of its scarcity and expense - was
being reused by multiple children forwashing themselves and for washing vegetables
found that the more people .used the contaminated water, the more likely they got
infected.
Bottled water users may have other risks washing vegetables with bottled water by
not doing as good of a job as washing them under running tap water.
Life style and health consciousness may be the primary confounders.
11.4 Randomized Community Trial >- Study Design Model
-Presented by Dana Flanders and Robert Oilman
Both Flanders and Oilman presented an outline of the Randomized Community Trial
study design. The goal of the study is to determine an estimated reduction of infection
due to increased treatment (i.e. filtration, UV, chlorination. Ozone) at a community level.
This study design has the benefits of a large sample size. It allows researchers to collect
blood or stool specimens door to door (if indicators miss disease symptoms they still
detect incidence of infection), look at broader community-wide indicators such as growth
and school attendance of children (most susceptible sub-population), and collect data
through mortality rates and sewage surveillance.
11.4.1 Method
1) Identify approximately 30 communities:
Homogeneous or matched pair: not too dissimilar in baseline rates of infection
and/or disease, type of water source/treatment/distribution system, population
characteristics such as size and age distribution.
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Meeting Summary
At least 6 communities would be studied per intervention group. The sample size
would be relatively large (# people in community * # of communities).
2) Identify households in each community
Distance from treatment plant (to identify effects of distribution system).
Possibly over-sample those near the source so that effects of the distribution
system might be minimized for this subgroup
High-risk sub-populations (children or immuno-compromised).
3) Measure baseline infection or disease rates.
4) Randomly select some communities for control. One group will receive early
intervention, the other late intervention all will eventually get water quality
improvements.
5) Measuring effects:
-Stool collected once per week (regardless of presence of symptom) and tested for
pathogens.
-Seaim collected - use of finger stick could reduce some of the public's
resistance.
Other data points and collection techniques:
-vomiting -- telephone
-doctor visits -- telephone
-birth weight -- telephone
-absenteeism -- telephone (school/work)
-growth ~ hospital visits
-mortality reported
Use hooks to convince people to cooperate: monitoring of children for free lor
anemia, growth, etc.
6) Outcomes:
Time to time variation within community prevalence/incidence between years.
natural waxing and waning within one community would be measured (this
- natural variation is important to understand for National Estimate. It measures the
noise of random variation between years.)
Time-to-time variation of household versus outside (office/school) exposure.
Meaningful because of randomization.
Outcomes would take 2 years (to account for variation in time and season)
Intervention studies present problems however, randomization solves many of
these problems.
Baseline and post-treatment: you get two years of "before and after" data.
Infection: studying infection is much more sensitive than looking for symptoms
.(diarrhea).
Check stool weekly whether or not there-is diarrhea. Dr. Calderon's experience
showed that people are willing to provide samples.
Get diarrhea rates by phone: collects both infection and diarrhea rates which is
another correlation the study would be collecting data on (disease rate / infection).
Incidence: you can compare directly those communities with good and bad water.
Interventions -Installation of filter at utility- study could still be randomized
because of large amount of plants making changes. Scientifically credible
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Meeting Summary
because you know and can account for the quality of water sources in
communities you are comparing.
7) Cost:
Many of the components of this study could be subcontracted out to reduce costs.
(Laboratory testing should cost around $3 / sample).
Infection costs could be reduced by sub-contractors (visit 1 time per month)
1 Testing for Cryptosporidium and viruses could be inexpensive if you leave out the
few pathogens that are particularly difficult and expensive to detect.
Cost to community of adding extra treatment for 10,000 is roughly 1 million
dollars.
-Lots of cities are currently putting in filtration/ozone ~ 100s of communities are
currently making changes, many are also remaining untreated, however;
-There may be other important differences between communities that choose to
change/upgrade their treatment methods and those that do not. It is feasible to
take list of communities making changes and randomize on this list -- this keeps
randomization with the bounds set by those making changes and those that arc
not.
11.4.2 Discussion
In summary this study design: /-
Uses and established epidemiological design, intervention at community-wide level.
Responds to the fact that there is no single method that will get attributable traction
number you need a mosaic, i.e. numbers of estimated waterborne disease cases vary
greatly.
Is inexpensive in comparison to the cost of changing technology to add observational
studies in changes that are already going on these communities making technology
changes are natural experiments that can be used for this study.
Workshop participants offered the following comments:
' The fundamental research question should be: what is the impact of drinking water on
GI illness and compare with water of little or no risk? The study would then use
"pristine" water and look at the absolute risk of drinking tap water.
This study answers the question of relative risk between different treatment
approaches.
It is also hard to eliminate problems of post-treatment reintroduction oi pathogens.
Just knowing the treatment technology (as unit of comparison between communities)
does not guarantee quality of water.
The issue of whether and how to blind people in the study was discussed at length. One
participant suggested that the following'criteria are used to determine when blinding is
necessary:. 1) blinding is necessary for the success of a study, and 2) blinding adds no
appreciable risk. Another participant stated that an open issue is how much will blinding
effect the results of the study? Oilman and Flanders responded that researchers,
laboratory and analysts must be blind ~ but it is questionable whether it is necessary or
even possible to blind the community. It is not clear whether the public will care or
change their behavior if they do know. In contrast to this view, one participant felt that a
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Meeting Summary
study on this scale would attract the media and political attention. In the case of
household treatment units it was pointed out that the taste of water will change and
people are likely to figure out which water has been treated and which is sham.
Another observation was that avoiding blinding of the community addresses many of
ethical considerations of epidemiological studies. A non-blinded study means
communities have a choice. One participant pointed out that if community that is not
getting intervention still gets equal medical care (i.e. baseline is not diminished) then
there are not ethical problems with an intervention study. For example, utilities make
changes all the time without public notice. However, another participant noted that the
EPA Administrator recently announced an effort to increase the public's "right to know"
about changes in water treatment methods by utilities.
II.5 Time Series Study Design Model
-Presented by Robert Morris, Tufts University
Robert Morris presented a Time Series design as a waterborne disease occurrence study
design. This approach evaluates the association between day to day changes in
community health indicators and changes in water quality over time in the same
community. Data on turbidity, presence of pathogens, and other water quality indicators
would be compared with community health indicators that are readily available in a
computerized form such as emergency room visits as recorded in medical billing data or
anti-diarrhcal sales. These data could be used to determine if short-term changes in water
quality are associated with increases in these indicators of gastrointestinal illness. This
approach eliminates all confoundcrs except those that vary in time with water quality.
Thus, the list of confounders is relatively-short and is primarily limited to factors that
demonstrate the same temporal variability as water quality. Morris explained that the
sample size could be as large as an entire city, depending on the data set used as an
indicator of gastroenteritis in the community.
estimating attributable fraction using this method would require two steps. First, the ,
time series method would be used to estimate the association between water quality and a
given health indicator. Then, the relationship between the specific health indicator and
the incidence of disease in the community could be examined. Finally, this information
could be combined to estimate disease risk in the community.
Coupling this method with planned cohort arid intervention studies would provide
important information valuable information on the relationship between health indicators
based on computerized data bases and rates of infection and disease among individuals in
the community. This information could help in the interpretation of time scries studies.
particularly with respect to attributable fraction.
One participant pointed out that, though turbidity may not be the best indicator of water
quality, it could be coupled with other information collected on pathogens and other
tested criteria. However, regulations are presently based on turbidity and so associations
between turbidity and health have direct relevance to these water quality standards.
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Meeting Summary
Morris then outlined the advantages and disadvantages of the Time Series study design.
Advantages:
Low cost (can look at many cities).
Short time to completion (could use historical data).
Can directly relate to indicators used in standard setting (could use changes in
turbidity or other indicators that are regularly measured).
May provide tool for long term surveillance (not expensive to maintain information
collection system once it is established).
Could extrapolate findings to National Estimate if method were validated by detailed
study in a few cities and then employed in a larger number of cities.
Confounders would have to be connected with water quality (temporal changes).
Can be used to study factors related to water source and water quality that influence
the association between monitoring data and disease.
Lots of things will cause GI illness but these studies should pick up those that are
correlated specifically with drinking water quality.
Analysis of the specific time lag between changes in water quality and changes in a
health indicator may be related to the incubation period for the infectious agent and
may be useful in identifying the responsible pathogen.
..£*.
«**
Disadvantages: ,^ .
Docs not relate individual exposure to outcome.
May be difficult to isolate effects of the distribution system. Stratification of the
population by distance from treatment plant might give some indication of this effect.
(Note that this is not the only study design that has this problem).
Rare events difficult to analyze.
Stage I rule may reduce efficacy of current surrogates for water quality such as
turbidity.
You need several years of data to deal adequately with seasonal effects in the data.
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III Approaches Towards A National Estimate
"Ron Hoffer, EPA, summarized the topics covered on the first day of the Waterbome
Disease Workshop in an effort to organize the discussion and to help participants
understand its scientific and policy context. Discussion then focused on the individual
study designs and extrapolation to the national estimate. The following section is
organized around the outline presented by Hoffer and discussed at the Workshop.
III.l Causative Factors & Site Selection
HI. 1.1 General
A participant noted that the National Estimate would not be helpful unless it included
information on the source or cause of contamination. He suggested that one way to
obtain this data is stratification of households by other variables such as distance from
treatment center (i.e. if the source of contamination is in the distribution system -
cither due to bacterial growth or exogenous pathogens - then the likelihood ot" being
exposed to contamination may be less closer to the plan).
According to one participant the dispersal of the pathogens in water is a central and
not very well understood component in estimating the risk of waterborne disease.
"This is a universe of distributions," these pathogens are not evenly distributed in the
water. Also, there is wide intra-populatron variability of resistance of humans and in
the virulence of pathogens. Another participant pointed out that there appears to be
disagreement of predicted risks versus measured concentrations of pathogens in
groundwatcr.
111.1.2 Source Water (Surface/Ground)
One participant noted that viral contamination had been documented in groundwatcr
sources and that future epidemiological studies should be sited in communities using
ground water.
This participant also suggested that the criteria for selecting water supplies tor study
should be made explicit.
A participant explained that Cryptosporidium has been noted in groundwatcr
(including in a supply associated with an outbreak in the UK.)
III. 1.3 Treatment Method/Technology
Another participant suggested that a consideration in evaluating the type and number
of studies should be on an understanding of the distribution and characteristics of
different types of water supplies and treatment/distribution systems including their
vulnerability to contamination.
More than one participant suggested that the utility industry would play a crucial part
in identifying the types of treatment that were being used and in helping researchers
choose which should be the focus of study.
III. 1.4 Reportability and Compliance
One participant explained that reportability of suspected waterbome illness - for
those cases that are reported on clinical suspicion - food borne infection is often used
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Meeting Summary
as general heading. This heading should reflect more specific separation among
water and food as the source.
This participant continued that because Cryptosporidium and Giardia are hard to
identify without a laboratory test, physicians should be encouraged to recognize their
symptoms and order tests for them when encountered.
III. 1.5 Site Selection
One participant suggested basing site selection decisions on information about current
risk. What characteristics present highest risk (what types of source, treatment,
distribution, etc.). However, countered another participant, highest risk areas make
up a very small percentage of the water systems in the US. Small community systems
are often least adequate, but they also serve a small population.
In response to a question an EPA representative pointed out that there are many
questions of practicality in how to measure water quality or identify contamination in
source water. It would be ideal to have at least one study in each category of water
source and treatment technique, but they have limited resources. In an environment
of limited resources, the economics of the situation dictate that the Agency must try
and achieve the "greatest bang for the buck."
The unit of organization is not clear - By water source, watershed, community, city
or sub-population. How do we find representative groups? Can we generalize
criteria used in one situation to others"(i.e. one type of system or sub-population?)
How do we characterize watersheds?' Need basis for broader representation.
Issues of site selection also involve criteria imposed by epidemiological study design
issues.
II 1.1.6 Choice of System and System Size
Levels of contamination and types of contamination (i.e. relation between turbidity
and pathogens) vary greatly between individual systems and by season and other
variables such as weather conditions.
Other participants mentioned their concern that the studies not focus exclusively on
large city systems. They noted the common assumption that large systems account
lor most infection, and pointed out the bias towards picking up outbreaks in large
systems. There may be correlation between system size, water source, the
population's immunity, and access to medical care, physician's ability to detect, and
likelihood of reporting an outbreak.
Federal regulations differ for large and small systems and it may make sense from
both a policy and science perspective to separate consideration of them. One
participant suggested that focus should be put on the system characteristics that serve
the largest percentage of the population. Another suggestion was to define simple
categories of sites. One participant suggested using either a weighted average (in
proportion to the number of people in each category) or taking a random sample of
the population by selecting individual characteristics (by source of water) and using
random matched pair comparisons.
An EPA representative pointed out that EPA has work to do before deciding how to
prioritize between water systems for the next set of studies.
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Meeting Summary
///. 1.7, Number and Types of Sites Needed for Portfolio
One participant suggested that ultimately 20 to 25 sites (not just the 5 mandated by
Congress) should be studied, once you start looking at different characteristics of
water systems there are many different characteristics you must consider: size,
source, treatment method, distribution system. Dr. Juranek explained that the CDC
will probably take rriore'than the mandated number of five sites because a wider
portfolio is needed. The national estimate is not the endpoint of the CDC/EPA effort.
It is crucial to obtain the help of experts from the water industry to understand what
types of water systems and which communities it would be useful to study.
One participant felt that there should not be one National Estimate number; "this
estimate should change over time going down as the amount of uncertainty
decreases and water quality improves."
This participant continued that a related goal is the development of tools and criteria
that are low cost and generalizable. Hoffer explained that EPA and CDC have
responded to this concern through their goal of creating a portfolio of studies and
approaches as a basis for a national estimate.
There is no single study that will come up with an acceptable risk estimate number.
The question, according to another participant, should be; what would be the suite of
studies that would be most helpful in arriving at national estimate?
111.1.8 Indicators of Exposure to Pathogens-and Disease
Another major point of discussion concecned the health endpoint that should be
measured. Participants discussed specific questions on which and how to measure
exposure to pathogens, immune response, infection, or disease directly and whether to
use indicators such as symptoms, medication sales, or behavior.
Many participants felt that pathogen specific testing offers the greatest confidence in
the results because it is able to test for stool positivity and serum antibody response
for suspected pathogens. Other participants, however, explained that this approach is
not entirely practical. It misses many, cases of infection because only approximately
10% of people suffering with gastrointestinal illness see a doctor and loss than 3%
. have stool tested for parasites or viruses. Also, no tests currently exist for many
waterborne pathogens.
One participant relayed their experience that it can be difficult to obtain the
specimens of blood needed for testing - especially from children. This participant, as
well as others are currently investigating the use of saliva as an alternative.
Specific pathogens, according to a participant, present individual problems in
monitoring. For instance, cryptosporidiosis is a relatively common infection. The
role of immunity affects our ability to study it. People at highest exposures and risk
of spreading infection often have lowest illness rates ~ visitors to an area may get
sick while immuno-competent residents (exposed regularly) are immune. This
participant explained that in this case, intervention studies could draw the wrong
conclusions (if trying to detect risk of infection). Looking for illness could be the
wrong place to look for exposure or risk of drinking water. This is further
complicated because we do not know how long immunity persists or the distribution
of Cryptosporidium in the drinking water systems.
Page 24
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Final WBD Workshop - Oct 9-10, 1997
Meeting Summary
We are looking at many pathogens with differing levels of understanding of their
virulence, symptoms, and health effects.
This participant suggested that age-restriction of the study population would make
wider sampling more feasible. The only criteria to limit the number of specimens
required that made sense was age-restriction those below the age of 10 have 60% of
the cases of infection of Cryptosporidium and those above 65 have very few cases.
Therefore, efforts should be concentrated on looking at children.
///. 1.9 Distribution Systems
Another concern brought up was the issue of pathogens coming from within
distribution systems. According to one participant it is imperative to understand the
source of pathogens in drinking water to truly understand and address drinking water
risk.
A number of participants brought up the concern that the focus on water sources was
missing other contributing factors within the distribution systems (i.e. pipe
contamination). The characteristics of the water distribution system and water supply
are crucial. Therefore the studies must ultimately identify the source of the risk and
focus on intra-system problems. Participants also discussed the potential role of
biofilms as a contributor to contamination.
///./. 10 Specific Pathogens - >'
One participant related that the FACA Committee had suggested concentrating more
effort on pathogen specific studies.
Need to add Cycloxpont to list of pathogens of interest
///. /. / / Immnno-Compromised Sith-Populations
According to Dr. Juranck a major question surrounding the choice of a study
population concerns the focus on monitoring the drinking water risk on immuno-
. compromised (such as AIDS or recent chemotherapy patients) and immuno-
competent persons. Some participants felt that the immuno-compromised sub-
population is at greatest risk for severe infection and therefore may not be
representative of a national estimate. Others suggested that the best approach is to
determine the sensitivity of immuno-compromised persons and utilize them as target.
or indicator populations. Other parties countered that focusing efforts on this
population may lead to policy implications limited to immuno-compromised
population.
There was a concern that the studies include sub-populations at highest risk in the
National Estimate in a meaningful way.
111.2 Societal Impact
111.2.1 Health Issues
What is the focus of studies; do they measure severe illness, mortality, or chronic
health effects?
I'agc 25
-------
Final WBD Workshop - Oct9-I0, 1997
Meeting Summary
Are studies sensitive to secondary effects: such as developmental issues or organ
dysfunction associated with infection that are not accompanied by acute effects (i.e.
diabetes associated with viral infection)?
Are the studies looking at endemic occurrence of WBD or outbreaks?
///. 2.2 Economic Issues
Health Care Costs
School or Workdays Lost
Unemployment
Lost Tourism Revenue; a participant mentioned that dollars lost due WBD outbreaks
cost the entire economy money (not just region). This study found that there is a
national net loss of economic gain from an outbreak (cancelled vacations)
Decreased Consumer Confidence
Avoidance costs (costs of switching to other water sources such as bottled water).
Administrative Costs of outbreak
A CDC representative mentioned that CDC is currently involved in an effort to study
the costs associated with WBD outbreaks:
III. 2.3 Equity/Justice Issues
Access is limited to alternative sources of drinking water (home bottled or filtered
water) because of high costs. These effects may be compounded because the same
communities may have limited access to Health care as well.
Who should the regulations protect and how should society protect imnuino-
suppresscd sub-populations.
111.3 Methods
III. 3.1 General
A participant suggested that for very little extra cost you could expand on-going
studies to get useful cpidemiological data. You may be able to get information on
specific pathogens tor little extra cost once you are doing other monitoring. For
instance, time series studies could be add-ons to the other studies. It is likely that
expensive studies will become the "gold standard" for developing, but would be
enhanced by cheaper studies in the same places to broaden knowledge on the many
variables involved.
Many participants recognized Dr. Calderon's effort to identify utilities that were
changing water sources or treatment methods and opportunities that should not be
missed to do "natural" experiments.
111.3.2 Case Control
The case-control design involves'identification of cases with infections that are
potentially waterborne and controls who do not have the disease. The exposures of
the groups are then compared to determine if the cases have a higher likelihood of a
given exposure.
Example: Persons with laboratory diagnosed cryptosporidiosis would be identified
together with a group of controls of the same age, race and sex from the same
Pace 26
-------
Final WBD Workshop - Oct 9-10, 1997
Meeting Summary
community. They would then be interviewed concerning their patterns of water use.
One might then be able to ask the question: Were persons with disease more likely to
have consumed tap water than persons without disease?
III. 3.3 Prospective Cohort
The cohort design involves identification of a group of persons who have different
levels of exposure to the risk factor of interest, in this case tap water. The cohort is
then followed over time to determine if the persons with the exposure are more likely
to become infected and/or develop disease.
Example: -A sample of persons living in a community is identified and interviewed
concerning their patterns of tap water consumption at home and at work. Over the
following year, they are asked to record any events during which they experience
symptoms related to gastroenteritis. At the end of the year, the rates of symptoms
among persons using exclusively bottled water is compared to those using exclusively
tap water.
111.3.4 Household Intervention
A set of households is randomly assigned to receive water that has undergone a
higher level of treatment than the tap water in those homes. These households arc
then followed over time. At the end;of the follow up periodl members of households
with this treated water are compared to members of households without the treatment
with respect to measures of infection and/or disease.
Example: A group of households is randomly assigned to receive cither a in-home
membrane filter or a box resembling the membrane filter. Over the following'year.
they are asked to record any events during which they-experience symptoms related
to gastroenteritis. At the end of the year, the rates of symptoms among persons using
home water filters is compared to those without home water filters.
///. 3.5 Community Intervention
This is similar to the household intervention except communities arc randomized to
receive improved treatment rather than households.
Ten similar communities are identified and 5 are randomly selected to receive
improved water quality treatment. These communities arc then followed for one year
to determine the incidence rates of gastroenteritis.
II 1.4 Study Scale- for National Estimate
The problem with looking for data on a national level is that it is extremely difficult
to extrapolate from one city to another because of the variability of drinking water.
variability of water, and demographic and other host factors.
Taking a national approach also limits other uses of data - smaller scale studies add
to our understanding and are useful in public health surveillance.
One participant suggested that the most efficient way of doing the national estimate
would be a national scale study that would randomly select sites fro,m specific
regions. This study would not be useful for extrapolating down to more specific data
on a regional level, but it might be the best way of avoiding the issues of site and sub-
population selection.
' Page 27
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Final WBD Workshop - Oct 9-10.1997
Meeting Summary
One participant felt that intervention and analysis may be better at community level.
One drawback is that you would need a larger number of communities to obtain
meaningful data. The number needed would depend on the amount of illness.
HI. 4.1 Scientific and Policy Credibility
The question of how the EPA extrapolates risk estimates of low levels of exposure
was asked by a number of participants. Regli explained how this estimate was the
result of "fitting" a dose response curve down to zero based on the available dose
response data points from different studies. One participant pointed out that although
it is understood that exposure to a single oocyst can lead to health effects, there are
huge intra-population differences in resistance to pathogens, different in the virulence
of pathogens and effects of exposure.
III.5 Next Steps
The final presentation of the WBD Workshop was by Emerson Lomaquahu from the
American Water Works Association Research Foundation (AWWARF) on a January
1998 meeting AWWARF and EPA are sponsoring on epidemiological studies related to
the development of a national estimate and possibilities for research funding. In closing
GDC and EPA representatives discussed how they would move forward with the
development of the national estimate. £ -
III.6 American Water Works Association Research Foundation
Emerson Lomaquahu gave a description of the American Water Works Association
Research Foundation's upcoming waterborne disease workshop. AWWARF is a private,
non-profit organization primarily supported by drinking water utilities, as subscribers.
that contribute to a centralized research program. AWWARF also collaborates with other
organizations such as EPA. One example of this collaboration is the
Microbial/Disinfection By-Product Council. This council has met annually over the last
two years to determine research needs and projects. It has allocated approximately S2
Million per year For research to support regulatory mandates. One project planned for
1998 is a workshop that will convene a multi-disciplinary group of experts to review
study designs of cpidcmiologic studies to estimate endemic diseases associated with
drinking water. The study designs will serve as a basis for possible future funding.
Lomaquahu closed by noting that the AWWARF would take nominations for candidates
to participate in the expert workshop.
Emerson Lomaquahu can be reached at AWWARF (303/347-6114).
III.7 Additional Site selection considerations and closing remarks
Fred Hauchman, EPA, proposed using a decision tree approach to answering the
questions surrounding the national estimate, in particular how to approach possible
differences in drinking water quality (and any associated disease) based on a number of
factors. The group also discussed the development of a study site selection matrix based
on broad categories of source water contamination (high/low) versus level of microbial
treatment (no/limited/excellent treatment). Information on source water quality and
treatment will become available within the next two years .from the results of the
Page 28
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Final WBD Workshop - Oct 9-10, 1997
Meeting Summary
Information Collection Rule, EPA's supplemental Ciardia and Cryptosporidium surveys,
and through an AWWARF/M/DBP Research Council project on the spurce water quality
variability. The AWWARF project involves the collection of frequent (daily) samples
for pathogens and water quality indicators. Participants discussed the feasibility of
selecting epidemiological study sites where treatment and water quality information
would be collected.
National Waterborne Disease Occurrence Estimate Decision Tree
Water Source ^ System Size ^ Treatment Technique
(surface/ground) (large/smalt) (filtration, chlorine, UV. etc.)
Considerations: study design, etiologies, water quality, demographics, seasonality, region, etc.
The meeting concluded with representatives from EPA and CDC thanking the
participants for their hard work and cooperation in making the Workshop a success.
According to one participant, the meeting had helped EPA and CDC identify new ideas
to ponder and put "different spins on old ideas."
I'acc 29
-------
WATERBORNE DISEASE WORKSHOP
October 9 and 10,. 1997
Meeting Summary
Attachments
Presentation Motes
A. Stig Regli Presentation Notes: Statutory Requirements
B. Jeffrey Griffiths Handout: Routes of Exposure / Spread and Detection of Waterbome
Infectious Disease
C. Dennis Juranek Presentation Notes:
1. National Estimate of Waterbome Disease Occurrence
2. Ongoing CDC Surveillance Systems Related to Water 1996
. 3. Incidence of Gastrointestinal Illness
D. Jack Colford Presentation Notes: Toward a National Estimate of Waterbome
Diseases: A Randomized. Triple-Blinded, Placebo-Controlled Trial of the Feasibility
of Household Drinking Water Intervention Studies
E. Rebecca L. Calderon Presentation Notes: Community Enteric Study - Enteric Disease
Study
Phase I - site selection
Phase II - site evaluation
Phase III - pilot(full scale)
F. Floyd Frost Presentation Notes: Survey Results from Paired City Study
Meeting Information
G. Agenda
H. Participant Ljst
-------
Attachment A
Stig Regli Presentation Notes:
Statutory Requirements
-------
Statutory Requirements Pertinent
to Microbiai DW Regulations
Must set maximum contaminant level
goal (MCLG) for contaminants of
concern
- set at level at which no known or
anticipated health effects occur & which
allows adequate margin of safety
- Current MCLGs under SWTR :
Giardia = 0. viruses=0
- Proposed MCLGs under IESWTR
Cryptosporidium = 0
Statutory Requirements Con'd
Must set MCLs or Treatment Technique
Requirements as close to MCLG as
feasible (considering costs)
Additional Considerations
- may be set at level other than feasible if
feasible level results in increase risk of
other contaminants in drinking water
level of treatment shall minimize overall
risk (balance risk) that may result from
treatment technique or MCL
-must be sensitive to cost/benefit analysis
Overview of Current Regulations
i Surface Water Treatment Rule (SWTR) "
- systems using surface water must maintain ,
> 99.9 percent removaUlnactivation of Giardia "
> 99.99 percent removal/lnactivaUon of viruses
turbidity monitoring & performance criteria
disinfectant residual In distribution system
- untutored systems meet watershed control &
source water quality criteria
i Total Conform Rule
- applies to all systems
all systems must monitor for conforms
< 5V. measurements can be positive
Possible Interim Enhanced
SWTR Criteria
> applies to systems with >10,000 people
all filtered systems must achieve >=99
percent removal of Cryptosporidium
-tighter filtration performance criteria
-monitoring of Individual filters
systems changing disinfection practice
to comply with Stage 1 D/DBP rule must
maintain exisiting levels of disinfection
-exceptions allowed through state approval
Regulatory Strategy for
Controlling Pathogens
' Develop criteria to adequately address
source water pathogen concerns
- control pathogens associated with causing
waterbome disease
- specify criteria that control for pathogens
most resistent to treatment
> Develop criteria to adequately address
distribution system concerns
Approach to Developing National
Risk Estimates
select target organism
- Cryptosporidium, Giardia. viruses
estimate national distribution of
concentration levels reaching consumer
- national source water distribution
- national level of treatment distribution
estimate infection rates from available '
dose response curves
- e.g., by extrapolation, person ingesting 1
oocyst has 2% likelihhood of being infected
estimate illness and mortality rates
-------
Attachment B
Jeffrey Griffiths Handout:
Routes of Exposure /
So read and Detection of Waterborne Infectious Disease
-------
JKG. RDM
TUSM:
Other animals
including pets
zoonotic
Routes of Exposure
Water
Food
Humans in a
different area
person to/person spread
\
N,
\
Target Human Population that is Exposed
to Cryptosporidium Oocysts
(Suppose 100,000 people are annually
exposed on an endemic basis)
Mild and moderate cases do not
seek medical attention
I
eed for fecal exam to be done
ced for fecal acid-fast or IFA test
Asymptomatic j
Infected
(75,000)
Symptomatic
(25,000)
Detected by
Medical System
(12)
Reported Case
(6)
Detection
2,500 seek medical attention [10% symptomatic 1
1,250 have a stool exam done [50%j
12 of these have an acid fast stain or IFA (.1%|
half are reported to the State [50% |
6/75,000 infected are reported: ~ 0.8/10,000
Of 100,000 exposed, 6 cases reported
-------
HO'.v MANY EXPOSURES TO C. P Ls.'.7.?.f .A:1£ THERE !N A Gi'/EN YI.AJ* FOR !>!£ US ?'"*Pr."LAT:o>.'"1
'-:!::. K Gn.LFiihs NLD MPH&TM National A<3oc:auon ot'?icpie \\\ih AIDS : :;' 3
A POTENTIAL BIAS IN THE LITERATURE IS THE BELIEF THAT SEROPREV\LENCE TO
THE TRANSMISSION (OOCYST) STAGE EQUATES TO THE CUMULATIVE TOTAL OF
PRIOR INFECTIONS.
Ungar e,i al' (1986) found that only 3 of 4 people immunologically competent people with known C. parvum
developed IgG lo.oocysi antigens, and the duration of response was < 4 months. In contrast, people with AIDS and
persistent infection had persistently (-) [gG.
Mead et al" found that serum anabody to sporozoites using Western blots decreased markedly over 5 months after
infection with C. parvum in immunocompetent people.
Moss et al1U obtained acute (3 -week) and convalescent (10 and 28 weeks) serum from Coast Guard personnel with
cryptosporidiosis after the 1993 Milwaukee outbreak. They tested for antibody using Western blots of oocysts. IgA.
IgM. and IgG to anu-oocyst antibody diminished markedly over time, and were usually gone by 23 weeks.
Groves et al (1994)" showed that anu-oocyst antibody peaks 3-6 weeks after documented infection, and falls to
baseline within a few months.
DuPont et at have infected human volunteers with CR." None of their seronegative volunteers developed persistent
IgG anti-oocyst antibody after infection, and only 40% developed any IgG anabody reaction to oocyst antigens
after a second infection (C. Chappell. pens comm: presentations to the EPA).
. This same transience of anu-oocyst antibody has been noted in other mammals."
No study has demonstrated that antibody to C. parvum, using oocyst antigen, is persistent except in '
chronically infected people with AIDS. In all studies that have examined this issue, antibody
responses (as measured with oocyst antigen) have been transient in the general population.
ANTIBODY TOTISSLTE STAGES. Individuals are only exposed to tissue stages (trophpzoites,
schizonts, and gametes) during infection, aqd so antibody to the tissue stages could be markers for
infection. Two published studies, and: one abstract, have tested for serum antibody to tissue stages.
T^ipo^ and Campbell in Scotland (1931)'" found - 86 %of adult blood bank scrum samples diluted 1:10 had
antibody to tissue stages using an indirect immunofluorcscent (IIP) assay, where scrum is reacted with tissue stages
in cryostat sections of infected animal intestine.
Campbell and Current (1983) reported thai after known infection. 12/12 immunocompetem people were tissue
anubody (~) using UF."U 7/7 were positive at 60-90 days, and 5/5 were still positive ai 360-iOO days. Here they
used dilutions of > \ 40 to exclude any false posiuves.
Ntiron et al at Rhode Island Hospital" prospecuvcly found - 45% of normal children aged 1-4 were ussuc anubody
I4-), matching the known pattern of infection in populations (Meinhardt et al 1996).' and that tins rate decreased
wiih age. \\hile antibody to oocysts increased with age.
Age Differences in Seroioqical Response* Oy Antigen
w
w
'0
w
w
i
40
so
10
9
1 10 1 y«M 00
I J 1 lo J mn oo
"i _ _ ^^
[J.....^««
.i7.il MM oa
* *""""»- '
1 1 «U v«tn aa |
) ' 1 .
a .
1
OOCY««*»1
-..«..
> 4 » 1
In cryostat sections of intestine, all
the life cycle stages of the parasite are
present. This means that all of the
antigens associated with infection are
available, not just those present in the
oocyst stage. Thus the Miron el al
study compares the age-related
occurrence of positive C. parvitm
antibody to a) the oocyst stage, and b)
all the life cycle stages.
-------
MANY EXPOSURES TO C. .-'. !/?& 7.?..' ARE THERE IN A GIVEN' YEAR FOR THE L'S POP'/LArCS"1
.'iilrc'. .; G.iiTi^s N!D .VPKiTM N'aucnal Association ot" People -A an AIDS "
REFERENCES
i Ungar BLP, Soave R, Payer R, Nash I Enzyme immunoassay detection immunoglobulin M and
G antibodies to Cryptosporidium in immunocompetent and immunocompromised persons. -I Infect
Dis 1986: 153.570.
ii Mead JR. Arrowood MJ. Sterling CR. Antigens of Cryptosporidium sporozoites recognized by
immune sera of infected animals and humans. Journal of Parasitoloev. 74:135-43, (1988)
iii Moss DM, Bennett SN, Arrowood MJ, et ai. (1994). Kinetic and Isotypic Analysis of specific
immunoglobulins form crew members with cryptosporidiosis on a US Coast Guard Cutter. J Euk;
Mjcrobioi4l:52S-55S.
iv Groves VJ, Lenmann D, Gilbert GL. (1994). Seroepidemiology of cryptosporidiosis in children
in Papua New Guinea and Australia. Epidemiology and Infection 113:491-9.
v DuPont, H.L., Chappell, C.L., Sterling, C.R., Okhuysen, P.C., Rose, J.B. and Jakubowski, W.
(1995). The infectivity of Cryptosporidium parvum in healthy volunteers. New England Journal of
Medicine 332:855-9.
vi De Graaf DC, Peeter JE. (1997). Specific interferon-gamma, IgA and IgM responses after
experimental infection of neonatal calves with Cryptosporidium parvum International Journal of
Parasitology 27 131-4
vii Tzipori, S and I. Campbell. (1981). Prevalence of Cryptosporidium antibodies in 10 animal
species. J Clin Microbiol 14:455-6.
viii Campbell PN, Current WL. (1983) Demonstration of serum antibodies to Cryptosporidium sp.
in normal and immunodeficient humans with confirmed infections. J Clin Microbiol 18:165-9.
* Miron D, Tzipori S, Flanigan T, Dennehy'P. Society for Pediatric Research abstract 1114, 1994
annual meeting.
' Meinhardt PL, Casemore DP, Miller KB (1996). Epidemiologic aspects of human
cryptosporidiosis and the role of waterbome transmission. [Review] Epidemiologic Reviews.
18(2): 118-36
xi Kuhls, T L., Mosier, DA, Crawford, D L. and Griffis, J. (1994). Seroprevalence of
cryptosporidial antibodies during infancy, childhood, and adolescence. Clinical Infectious Diseases
18,731-5.
xii Zu, S X., Li, J.F.. Barren, L.J , Fayer, R., Shu, S.Y , McAuliffe, J F., Roche, J.K. and Guerraiit
R.L. (1994) Seroeptdemiologic study of Cryptosporidium infection in children from rural
communities of Anhui, China and Fortaleza, Brazil. American Journal of Tropical Medicine &
Hygiene 51. 1-10
-------
Attachment C
Dennis Juranek Presentation Notes:
1. National Estimate of Waterborne Disease Occurrence
2. Ongoing CDC Surveillance Systems Related to Water 1996
\
3. Incidence of Gastrointestinal Illness
-------
Waterborne Disease Workshop
October 9-10, 1997
National Estimate of Waterborne Disease Occurrence
Ongoing CDC Surveillance Systems
Related to Water 1996
Incidence of Gastrointestinal Illness
Or. Dennis Juranek
Center for Disease Control
-------
National Estimate of
Waterbome Disease
Occurrence
A Daunting Task
Congressional Mandate
EPA and CDC conduct studies in at least five
cities to denve a national estimate of
waterbome disease occurrence.
Interpretation - Concentrate on microbiological
constituents in water, both well-know and
'emerging" bacteria, viruses, and protozoa.
Important Questions
What populations are at greatest nsk? £
What is the impact of waterborne disease?
Which infectious agents cause waterbome
disease? What is their relative contribution?
What are the characteristics of water
systems that are more likely to lead to
waterbome disease?
Workshop - March 1997
Purpose - to discuss the design and management
of waterbome disease occurrence studies
Attendees - specialists from:
-CDC
-EPA
- State Health Departments - Emerging
Infections Programs i,HP)
Emerging Infection Programs
7 sites - CN, NY. MD, GA. MM, OR, C A
Competitively chosen
Existing resources - FoodNet - surveillance
for enteric pathogens and GI illness
Funding considerations
Study Population
HIV positive
- Greatest nsk for severe infection
- Not representative
- Policy implications only for
immunocompromised
[mmunocompetent
-More representative seventy, demographics
- Broader policy implications
-------
Case Ascertainment Bias
Who gels included as a case? Are
cases representative?
-Severe cases
- Immune-compromised populations
-Health care access or behaviors
Study Characteristics
Confounding - Distortion
* -y
Alcohol consumption. ^^ Lung cancer
\
Cigareoe smoking
Confounding
Drinking Bottled
Water
\
Gastro intestinal
Illness
Healthy Behaviors
(e.g. hand washing.
cooking practices)
Study Characteristics
Number of Participants Needed
1 When is a negative study meaningful?
1 If we believed that drinking up water caused
no more than 1% of GI illness we would need
to study over 50.000 people to prove it
' Assumption - (he attributable fraction of GI
illness due to drinking tap water may be
between 10% and 30%
-------
First Steps
Cross-sectional studies using EIP sites
Feasibility study of household interventions
to assess:
- Blinding to intervention
- Effectiveness of the intervention device
- Point of entry vs. point of use
- Identify logistic obstacles
- Data collection tools
- Accessing human specimens
Selection of First Site
Municipality of > 100,000 persons
Surface water source
Evidence of fecal contamination of source
Conventional water treatment (coagulation.
flocculation, sedimentation, filtration)
Representativeness?
Different populations
Source waters (ground vs. surface)
Levels of contamination
Types of pathogens
Treatment technologies
Distribution svstems
Gl Him
Drinking
Water
Pathogen
(e.g. Cryptospondium)
Gaining Understanding and Clues
Attributable traction
Incidence/impact of Gl illness
IEtiologic agents
Association of water qualitv
indicators and Gl illness
Water consumption habits
-------
Ongoing CDC Surveillance Systems
Related to Water 1996
Water-Borne Disease Outbreaks
Cryptosporidium
CDC
Water-Borne Disease Outbreak Surviellance
CDC's and EPA's Objectives
Characterize epidemiology of wetartoonw dteeaae
outbreak* (WBDOe)
ldonttty«tiologlc agents of WBDOe and determine
why WBDOe occurred
terey
Identify typea of i
WBDOe
Train public heeMn penonnel how to detect and
InveettaateWBOOa
Cottab
i local
federal, and
International agenda* on InWattv** to prevent
*
CDC
Waterborne Obease Outbreak Surveillance involves
systematic
collection
analysis
interpretation
dissemination
of health related data.
Water-Borne Disease Outbreak
Surviellance
« Paaatv* avatun with annual aoilcitation of
report*
State and Local Health D«pf a collect data
«Voluntarily thare data with CDC
EPA provides supplemental water treatment
data
CDC
CDC
Limitations
l Passive system:
Sensitivity: probably low
Actual number of WBDOs unknown
Primary cause of under-reporting
probably under-recognition
Lengthy delays in recognizing & reporting
CDC
Factors that affect whether WBDOs ;
are recognized and investigated: \
i
Size of outbreak
Severity of disease caused by outbreak
Public awareness that an outbreak may be
occurring .
Investigator's Interest In studying the etiologlc
agent
Health department resources
Routine laboratory testing for pathogen c
-------
Approaches to Cryptosporidiosis
Surveillance
Make Cryptosporidiosis Rcporuble
Monitor Laboratory Diagnoses (Cryptoiporidium)
Monitor Sales of Antidiarrheal Medication (diarrhea)
Monitor HMO and Hospital Logs (diarrhea)
Monitor Nursinf Homes (diarrhea)
Combined Disease and Water Quality Surveillance
CDC
Surveillance for Cryptosporidium
December 1994: CSTE recommends that
Cryptosporidium be made a nationally
notifiable disease
36 states make Cryptosporidium a
notifiable disease
January 1995: States begin notification
CDC
Make Cryptosporidiosis Reportable
Strengths:
EitablUao nrimate of cnialmim aainbcr of cmio "
Serves u bu«4ia« 1111011 which increased anrnbcn
may be compared
Weaknesses:
Doci not improve diafnoau or rtpordof by payikiau
Do«i not inert*** roatiae lib taoaf
Mo*t likely to reflect infection* ia imniaocompromued
CDC
1995 National Survey of LaboretortM:
Cryptosporidium Tcating Indications and PrtctJc**
94 Labs contacted In 36 States
Test ail O&P stools routinely:
Test some stools:
* At the nqaesl of a pkyitdaa: (74)
(35 labi toted o«ty at pfepciu reqaot)
* All HIV+ per***: (8)
(7)
Do not test
5
74
15
CDC
Number of Cryptoaporl&um ca*«*
reported to COG by «tat», U3,199S
Current Surveillance Systems
Strengths:
la >M«| din
Bmlt*
Oiu »ran«< i kijuncal (rmm* *( nfanrc*
Weaknesses:
CDC
>M >nn«« aa Mdaiau W udMal riih fraai diiaktof w«ar
-------
Incidence of
Gastrointestinal
Illness
Cross-sectional Studies
Cleveland, Ohio
1948-1957
443 persons in 86 middle and
upper class families
1.34 episodes of diarrhea
and/or vomiting per person
peryear
Tecumseh, Michigan
1965-1971
y
Non-random sample of 4905 persons in 850
young families
0.98 episodes of vomiting and/or diarrhea per
person per year
1.9 episodes per year tn children < 5 years
Garthnght ec. Al. - Age-adjusted national
estimate of 0.62 episodes per person per year
Household Intervention Studies
Payment et. al.
Tap water drinkers
Age groups # of episodes per year
-0-5 years i.54
'-6-20 years . 078
-21-49 years 068
-50-t-vears 023
Emerging Infection Programs
14.7 million people, 6 Vo of the U.S. population
FoodNet Surveys
1996 - five sites - CA. OR. MM. GA. CT
Random digit dial surveys
Diarrhea! illness (> 3 loose stools in 24
hour period)
750 interviews per mondi; > 9000 per year
-------
Attachment D
Jack Colford Presentation Notes:
Toward a National Estimate of Waterborne Diseases:
A Randomized. Triple-Blinded. Placebo-Controlled Trial of
the Feasibility of Household Drinking Water
Intervention Studies
-------
Waterborne Disease Workshop
October 9-10, 1997
Toward a National Estimate of Waterborne Diseases:
A Randomized, Triple-Blinded, Placebo-Controlled
Trial of the Feasibility of
Household Drinking Water Intervention Studies
Dr. Jack Colford
University of California, Berkeley
School of Public Health
-------
10/07/97 TVE 10:23 FAI 643 3163 SPH EPI/SIOSTAT
Toward a National Estimate of Waterborne Diseases:
A Randomized, Triple-Blinded, Placebo-Controlled
Trial of the Feasibility of
Household Drinking Water Intervention Studies
Participating Institutions/Agencies/Individuals
University of California, Berkeley (UCB), School of Public
Health (Jack Colford, Art Reingold, Judy Rees, Asheena
Khalakdina)
California Department of Health Services and Emerging
Infections Program (EIP), (Due Vugia)
?A.
«J*
California Department of Health Services, Office of Drinking
Water (Cliff Bowen)
University of California San Francisco (UCSF), School of
Medicine (Joan Hilton)
Environmental Protection Agency (EPA), (Rebecca Calderon)
Centers for Disease Control and Prevention (CDCP), (Bill
Mackenzie)
-------
1Q/07/97 TUE 10:23 FAT 643 3163
SPH EPI/BIOSTAT 31004
Study Design: Overview
Randomized, placebo-controlled: Participants are randomly
assigned to receive either:
> water treated at home by special devices (see below)
OR
*> their usual water passing through a sham treatment device
Triple-blinded: Knowledge of the group (active device vs. sham
device) to which a participant is assigned will not be known by: 1)
the participant (single-blinding); 2) the investigators (double-
blinding); nor 3) the statistical team (triple-blinding).
Intervention groups: Households using devices to treat home
drinking water
f*-. .'
«*
Placebo groups: Households using inactivated devices that
resemble the active device in every visible external characteristic
Duration: 4-6 months in year 1; ideally 12 months for each
participant in years 2/3.
-------
10/07/97 TIT 10:24 FAI 643 5163 SPH EPI/BIOSTAT 3)008
Study Design: Specific Outcomes to be Measured
Year 1 ,
blindine effectiveness (can patients correctly identify the group
to which they are assigned). If not, a blinded trial is not
possible and this study design is not be appropriate for future
work. Blinding specifically to be quantitated using a previously
published index from the clinical trial literature.
costs of conducting the trial (i.e. is it likely the trials can be
conducted at other (at least 5) sites at a reasonable cost
health outcomes: nausea, vomiting, diarrhea, days lost from
work, visits to physicians,."highly credible gastrointestinal
illness" (HCGI) index used by Payment
laboratory outcomes: goal is to obtain blood, stool, and saliva
(using a home nursing agency) from all subjects during episodes
of illness. Specimens to be sent for testing to EPA/CDC.
recruitment and retention effectiveness (participant enrollment
and dropout rates)
Years 2/3
expand the study with respect to the number of cities/towns
under investigation (to meet Safe Drinking Water Act mandate)
use estimate of health and lab-confirmed outcomes obtained
during year 1 to generate appropriate sample sizes for the
studies in years 2-3.
-------
10/07/97 TUE 10:24 FAI 643 5163 SPH EPI/BIOSTAT
Study Design: Advantages and Disadvantages of a
Randomized Trial (cont.)
Disadvantages of this design
Cost
Labor intensive
Require much more time to conduct because of the need to
recruit participants, obtain permission from (multiple)
Institutional Review Boards (human subjects committees),
-------
Study Design: Intervention Devices and Groups
Comment: Preliminary bids received for grant preparation; final
bidding process to be conducted with EPA / CDCP guidance
Sample size: 38 families in each of the four groups (152 total)
powered to detect effectiveness of participant blinding
-------
Study Design: Intervention Devices and Groups (cont)
Comparisons to be made
Note: In a properly randomized and conducted trial, any
difference between two groups is attributable to a difference in
the controlled exposure (in this case the exposure is the drinking
water used at home by the participants)
Comparison #1 (Effectiveness of point of entry devices)
*> Rate (cases / person / year) of disease in Arm 1A versus Rate
of disease in Arm IB
Comparison #2 (Effectiveness of point of use devices)
> Rate of disease in Arm 2A versus Rate of disease in Arm 2B
-------
Study Design: Participants
Eligibility criteria
household consisting of at least one adult and one child age 2-10
detailed informed consent completed
household does not currently use bottled or specially filtered
water at home (nor have plans to begin use during the study)
type of drinking water used outside the home is NOT of concern
(such water consumption will be recorded in our data but in a
randomized trial is not likely to differ between the treatment
group and the placebo group)
Recruitment Strategies
randomly identified and Recruited by telephone by a CDC
contractor
$50 payment after initial enrollment and informed consent
$10 credit for each of the next 15 weeks
whether subjects are permitted to keep devices at the end of the
trial is a debated point
-------
Study Design: Sites
Process
interaction between primary study team, EPAV and CDC to
identify sites in California with the following characteristics:
*
water supply currently meets all drinking water standards
moderate to large urban area (> 100,000 population)
reasonable distance from principal study team (to minimize
travel budget)
preferably within the area of the California Emerging
Infections Program (pre-existing close working relationship
with these county health departments)
potential for logical expansion of the study at this site in
years 2/3
-------
FAQs: (Frequently Asked Questions)
What about the participants* consumption of drinking water
^^^_MM_M^^-.,^M^__MVi^B*^B.^MB«B_^»^^li^MMBl-^*M^^^1^^^^^M^^^^^^MMBB^* ,
outside their homes?
unlikely to differ between two randomly allocated groups of
participants
introduces a "conservative bias" (i.e. any results obtained are
likely to underestimate the magnitude of the difference)
What about specific infections?
specific viruses, parasites, and bacteria will be studied to the
extent that funding is arranged to test the specimens collected
during the study
-------
More FAQs: (Frequently Asked Questions)
What about generalizabilitv to other communities throughout the
US? -
all scientific evidence needs to be replicated (regardless of study
design)
one outcome of this study could be a standardized approach for
responsibly examining the health effects of drinking water in
communities across the US
Are the costs of the study unreasonable?
What are the costs of not properly addressing the question of
drinking water safety?
On the scale of costs faced by local utilities in making decisions
about water safety, the costs of properly conducted trials are far
below the radar.
-------
Background
Workshop on Design of Waterborne Disease Occurrence
Studies (Atlanta, March 12-13,1997) sponsored by USEPA and
CDCP (R. Calderon, F. Hauchman, R. Hoffer, S. Binder, W.
Mackenzie)
Workshop on Drinking Water and the Risk of Cryptosporidiosis
(Atlanta, June 1996) sponsored by the American Water Works
Association Research Foundation (AWWARF) (D. Juranek
CDC and S. Leonard-SF Water Dept)
Canadian trials of household drinking water intervention
(randomized but not blinded) (P. Payment et al.)
w
Safe Drinking Water Act (1996) charge to EPA/CDC:
> within 2 years after the date of enactment of this section,
conduct pilot \vaterborne disease occurrence studies for at
least 5 major US communities or public water systems
-------
Attachment E
Rebecca L. Calderon Presentation Notes:
Community Enteric Study - Enteric Disease Study
Phase I - site selection
Phase II - site evaluation
Phase III- pilot (full scale)
-------
COMMUNITY ENTERIC STUDY
Rebecca L. Calderon
Epidemiology & Biomarkers Branch
NHEERL
USEPA
ENTERIC DISEASE STUDY
Phase I - site selection
Phase II - site evaluation
Phase III - pilot (full scale)
-------
RATES OF ENTERIC DISEASE
'., ,
Longitudinal study - dai\
y
»>300 families
^children between 2 and 10
Surveillance
^Nursing home surveillance
»>Hospital admissions
^Clinical lab reporting
^Antidiarrheal sales
^Cross section serosurvey
^HMO/nurse hotlines
^(School absentees)
-------
COMMUNITY ENTERIC DISEASE STUDY
Goal: Obtain information on enteric disease rates in the United States.
Enteric disease rates are needed to determine environmental health
policy and management strategies for environmental sources of
microorganisms.
Objectives:
Determine the enteric disease rates in various communities
across the country.
Determine the relative source contribution of environmental
factors associated with enteric disease.
Determine etiologic agents associated with enteric disease.
Evaluate methods of surveillance.
# '
Background:
Mlcrobial organisms that cause enteric disease and their sources are a major
concern for EPA. To conduct risk assessments or determine environmental health policy,
information Is needed on the level of disease, factors that influence that level, specific
microbial organisms that cause illness, and possible sources of those organisms.
Approximately 50% of food and waterbome disease outbreaks are of unknown etiology.
Current surveillance programs do not provide adequate information on background rates of
enteric illness and the relative source contribution of environmental sources of organisms
that cause disease. In addition, current surveillance does not provide information on the
effectiveness of environmental policy or management decisions in lowering exposure or
reducing disease.
Proposal:
This project will conduct an enteric disease study in several communities
across the United States looking at various ranges in environmental parameters. These
studies would determine endemic levels of disease in the community and determine the
relative source contribution of known environmental factors. In addition, assess .efforts to
identify etiologic agents (known and unknown) responsible for symptomatology.
Studies will examine alternative surveillance methods versus longitudinal
studies as means to obtain information for trend analysis.
Site selection. To vary environmental ranges of environmental factors, communities of
different geographic location, size, drinking water sources and drinking water treatment
have been identified. Ideal communities would be those served by utilities that are about
-------
Attachment F
Floyd Frost Presentation Notes:
Survey Results from Paired City Study
-------
Waterborne Disease Conference
October 9-10, 1997
Dr. Floyd Frost
Lovelace Medical Foundation
Center for Health and Population Research
-------
10/08/97 WED 10:54 FAI 505 252 7043
LOVELACE R£SPIR RESRCH
(3302
Ground Water-Albuquerque
Greater than 35% of Positive Control(%)
1: What is your age:
Age Frequency
<30 19
3 MO 60
41-50 68
51-60 40
61+ 11
P
2: What is your sex?
Sex Frequency
Male 99
Female 101
P"
3: What is your race?
Race Frequency
White 160
Black 2
Asian 3
Hispanic 27
Other 8
P"
4: Are yon married?
Married Frequency
Yea 140
No 60
P-
5: Are you an Albuquerque
Resident Frequency
Yes 165
No 35
27H
15.79
36.67
39.71
27.5
54.54
0.41
27H
37.37
31.68
0.32
27H
35
0.
*.
«y
33.33
- 37.04
JK
Z3
0.82
27H
37.14
28.33
0.22
resident?
27H
34.54
34.29
0.92
27A
10.53
23.33
25
17.5
36.36
0.68
27A
28.28
15.84
0.07
27A
23.13
Q
v
25.93
o
0.42
. 27A
23.57
18.3
0.46
27A
21.21
25.71
0.26
17H
10.53
25
22.06
25
54.54
0.44
15/1 7H
27.27
20.79
0.45
15/17H
23.75
0
Q
25.93
37.5
0.64
15/17H
27.14
16.67
0.19
15/17H
22.42
31.43
0.39
17A
10.53
13.33
16.18
12.5
36.36
0.36
15/17A
15.15
14.85
0.89
15/17A
15.63
0
n
w
14.81
12.5
0.83
15/17A
15.71
13.33.
0.65
15/17A
13.94
20
0.42
w
6: Length of residence (years)
27H
27A
17H
17A
Length
1-4
5-9
10-14
15-24
25+
Frequenq
33
^K f
25
31
30
46
P
7: Where does your household
Source Frequency
City Water 166
PvL Well
1
f *
35.29
^7
jL
40.63
34.48
30.43
0.97
water come
27H
35.54
<** . .
25
20
21.88
24.14
17.39
0.94
from?
27A
23.49
o
26.47
20
28.42
24.14
19.57
0.60
15/17H
22.29
0
16.18
20
18.75
6.9
13.04
0.29
15/17A
13.86
0
-------
10/08/9T WED 10:55 FAX 505 262 7043
LOVELACE RESPIR R£SRCH
(21003
Other 11
Cityw/filter 13
Pvt.Well/Strut 8.
Not sure 1
18.18
38.46
37.5
0
0.76
9.09
30.77
0
0
0:46
p-
8: Do you work or got to school in a different city?
*.
Work/School Frequency
Yes 33
No 167
27H
30.30
35.33
0.72
9! Do you regularly drink bottled water?
Bottled Frequency
Yes 39 33-33
25T
10: Do you use bottled water to make ice?
Ice Frequency 27H
Yes 8 50
No 192 33f5
OJ8
U: Do you use bottled water to wash food?
Wash Frequency 27H
2 50
198
27A
18.18
22.75
0.50
27H
27A
20.51
26.09
0.85
27A
37.5
21.35
029
27.27
38.46
37.5
0
0.58.
15717H
30.3
22.75
0.33
18.18
23.08
25
0
0.89
15/17A
24.24
13.17
0.16
15/17H
15/17A
27A
50
21.72
0-35
U: Do you have children in your household ^de"8e 5?
Children Fluency m ^
No* m 33f . 2?
P13:ln the past 12 months, have you had a child in your house
Day Care Frequency OT ^
M" H7 33-9 20'34
No 177 Q67 012
f4:ln the past 12 months, have you handled a child with diap
Diapers Fluency 27H ^
M" m 38-02 24-°°
No 121 QJO 0.66
r5:ln th. P«t 12 months, have you cared for someone with c
Cared For Frequency ^ .^
M" m 33-33 2L64
No 171 04J 0.44
20.51
29.19
023
17H
37.5
23.44
OJ3
17H
50
23.74
OJ7
15/1 7H
31.03
22.81
0.27
attend day
15/17H
39.13
22.03
0.05
A
iers?
15/17H
21.52
25.62
0.72
i * * - *^
liarrhea?
1S/17H
37.93
21.64
r>04
15.38
19.87
0.64
17A
37.5
14.06
0.08
17A
50
14.65
0.18
15/17A
17.24
14.62
0.41
care?
15/17A
26.09
13.56
0.14
1S/17A
15.19
14.88
0.73
15/17A
27.59
12.87
0.01
-------
10/08/97 W£D 10:53 FAI 505 2S2 7043
LOVELACE RESPIR RESRCH
@Q04
16:In the past 12 months, have you handled pets (cats, dogs)?
Pets Frequency 27H 27A 15/17H
Yes 172 " 32.56 20.35 22.09
No 28 46.43 32.14 35.71
p- 0.18 0.17 0.22
17: In the past 12 months, have you handled young pets (less than 1 year old)?
Young Pets
Yes
No
P~
Frequency
75
125
27H
38.67
32
0.27
27A
28
18.4
0.12
15/17H
28
21.6
0.36
18:In the past 12 months, have you handled livestock or zoo animals?
Livestock Frequency 27H 27A 15/17H
Yes 37 , 35.14 21.62 29.73
No 163 34.36 22.09 22.7
p- 0.90 0.99 0.46
15/17A
15.12
14.29
0.&4
i
15/17A
18.67
12.8
0.35
15/17A
16.22
14.72
0.84
19:In the past 12 months, have you drunk untreated water from lakes, streams?
Drunk
Yes
No
Frequency
11
189
27H
45.45,
33.8,6
0.46
27A
27.27
21.69
0.75
15/17H
45.45
22.75
0.07
15/17A
36.36
13.76
0.05
20: In the past 12 months, have you swum in a lake, stream, or public pool?
Swum Frequency 27H 27A 15/17H 15/17A
Yes 88 37.5 26.14 29.55 18.18
No 112 32.14 ' 18.75 19.64 12.5
p- 0.36 0.22 0.11 0.20
21:In the past 12 months, have you traveled out of the United States?
Traveled Frequency 27H 27A 15/17H 15/17A
Yes 42 50 35.71 38.1 23.81
No 158 30.38 18.35 20.25 12.66
p- 0.02 0.02 0.03 ' 0.10
22: In the past 2 months, have you had diarrhea (3 or more loose bowel movements a day)
lasting 4 or more days?
Diarrhea
Yes
No
Not sure
P-
Frequency
7
192
1
27H
57.14
33.85
0
27A
42.86
21.35
0
0.17
15/17H
0
25
0
0.14
15/17A
0
15.63
0
0.25
-------
10/03/97 WED 10:55 FAI 505 262 7043 LOVELACE RESPIR RESRCH ^005
Ground Water- Las Vegas, iNV
1: What is your age:
Greater than 35% of Positive Control (%)
Age
<30
31-40
41-50
51-60
61 +
P-
2: What is
Sex
Male
Female
p=
3: What is
Race
White
Black
Hispanic
Asian
Other
P- ''
4: Are you
Married
Yes
No
P~
Frequency
30
50
72
34
14
your sex?
Frequency
89
111
your race?
Frequency
180
6
2
10
2
married?
Frequency
105
95
27H
30
48
41.67
52.94
35.71
0.37
27H
3483
49.55
0.04
27H
42*22
66'67
0 *
50
50
0.53
27H
40.95
45.26
0.54
27A
20
44
33.33
44.12
35.71
0.21
27A
30.34
4054
0.14
27 A
36.11
50
0
30
50
0.74
27A
35.24
36.84-
0.81
17H
26.67
38
40.28
47.06
57.14
0.32
17H
34.83
44.14
0.1S
17H
39.44
50
50
50
0
0.72
17H
40.95
38.95
0.77
17A
20
36
33.33
35.29
57.14
0.19
17A,
26.97
39.64
0.06
17A
33.33
50
50
40
0
0.71
17A
38.09
29.47
0.20
5: Are you a Las Vegas resident?
Resident
Yes
No
P-
6: Length
Length
1-4
5-9
10-15
16-24
25+
P- .
Frequency
187
13
of residence (yean)
Frequency
48
42
20
35
42
27H
42.24
53.85
0.41
27H
35
38.09
64
48.39
42.86
0.27
27A
35.29
46.15
0.43
27A
31.67
33.33
48
45.16
30.95
0.58
17H
39.15
46.15
0.64
17H
40
33.33
62.5
41.94
33.33
0.42
17A
33.33
38.46
0.73
33.33
28.57
52
35.48
28.57
0.63
17A
7: Where does your household water come from?
Source Frequency 27H 27A 17H 17A
-------
10/08/97 WED 10:55 FAI 505 262 7043 LOVELACE RESPIR R£SRCH
@ O'P 6
City Water 143
Pvt. Well @ pond I
Cityw/filter 33
Pvt. well 8 -
Other 7
Not sure 8
P~
41.26
100
54.54
50
42.86
12.5
0.26
8: Do you work or go to school in a different
Work/school Frequency
Yes 15
No 185
P*
27H
46.67
42.7
0.77
34.97
100
45.45
25
42.86
12.5
0.35
city?
27A
46.67
35.14
0.37
35.66
100
51.51
37.5
71.43
37.5
0.19
17H
40
40
1.0
28.67
100
45.45
37.5
71.43
37.5
0.07
17A
33.33
34.05
0.95
9: Do you regularly drink bottled water?
Bottled Frequency
Yes 100
No 100
P~
10: Do you use bottled water to
Ice Frequency
Yes 38
No 162
P"
11: Do you use bottled water to
Wash Frequency
Yes 9
No 191
p-
12: Do you have any children in
Under 5 Frequency
Yes 28
No 172
P~
13: In the past 12 months, have
Day Care Frequency
Yes 19
No 181
P-
14: In the past 12 months, have
Diapers Frequency
Yes 71
No 127
P"
27H 27A
46
40
0.39
make ice?
27BL
3421
45.86
0.22
wash food?
27H
66.67
41.88
0.14
38
34
0.56
27A
26.31
38.27
0,17
27A
44.44
35.60
0.59
40
40
1.0
17H
42.1
39.51
0.77
17H
88.88
37.7
0.002
17H
32
36
0.55
17A
34.21
33.95
0.98
17A
66.67
32.46
0.03
your house under age 5?
27H
42.86
43.02
0.99
27A
39.29
35.47
0.70
you had a child in your house
27H
52.63
42
0.37
you handled
27H
43.84
42.52
0.86
27A
52.63
34.25
0.11
17H
39.29
40.12
0.93
attend
17H
47.37
39.23
0.49
17A
35.71
33.72
0.84
day care?
17A
47.37
32.6
0.20
a child with diapers?
27A
35.62
36.22
0.93
17H
45.21
37
0.25
17A
39.73
30.71
0.19
17A
IS: In the past 12 months, have you cared for someone with diarrhea?
Cared Frequency 27H 27A 17H 17A
-------
10/08/97 *ED 10:58 FAI 505 252 7043 LOVEUCE RESPIR RESRCH
Yes 30 36.67 33.33 33.33 26.67
No 170 44.12 36.47 41.18 35.29
P- 0.45 0.74 0.42 0.36
16: In the put 12 months, have you handled pets (cats, dogs)?
Pets Frequency 27H 27A 17H 17A
Yes 162 43 83 37.65 38.89 33.95
No 38 39.47 28.95 44.74 34.21
P- 0.63 0.31 0.51 0.98
17: In the past 12 months, have you handled young pets (less than 1 year old)?
Young pets Frequency 27H 27A 17H 17A
Yea 56 51.79 39.29 48.21 42.86
No 144 39.58 34.72 36.81 30.56
p- 0.12 0.33 0.14 0.10
18: In the past 12 months, have you handled livestock or zoo animals?
Livestock Frequency 27H 27A 17H 17A
Yes 10 30 30 30 30
No 190 43.68 36.31 40.53 34.74
p- 0.39 0.69 0.31 0.34
19: In the past 12 months, have you dfunk untreated water from lakes, streams?
Drunk Frequency 27H 27A 17H 17A
Yea 10 30- 30 30 20
No 190 43.68 38.33 40.53 34.74
p- 0.39 0.69 0.51 , 0.34
20: In- the past 12 months, have you swum in a lake, stream, or public pool?
Swum Frequency 27H. 27A 17H 17A
Yes 72 100 83.33 66.67 66.67
No 128 41.24 34.54 39.18 32.99
p- 0.02 0.03 ' 0.33 0.19
21: In the past 12 months, have you traveled out of the United States?
Traveled Frequency 27H 27A 17H 17A
Yes 33 41.67 27.78 37.5 30.56
No 167 43.75 40.63 41.41 35.94
p- 0.87 0.09 0.67 0.30
22: In the past 2 months, have you had diarrhea (3 or more loose bowel movements a day)
lasting 4 or more days?
Diarrhea Frequency 27H 27A 17H 17A
Yes 11 54.54 36.36 36.36 36.36
No 180 41.11 34.44 38.89 32.78
Not Sure 9 66.67 66.67 66.67 55.56
p- 0.70 0.39 0.70 0.69
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Attachment G
AGENDA
Environmental Protection Agency
and
Center for Disease Control
WATERBORNE DISEASE WORKSHOP
October 9 and 10, 1997
-------
Waterborne Disease Occurrence Workshop
October 9-10, 1997
Washington National Airport Hilton
2399 Jefferson Davis Highway
Arlington, Va. 22202
703/418-6800
Agenda
Workshop Objectives:
provide background on the Safe Drinking Water Act mandate to carry out
waterbome disease occurrence studies and develop a national estimate of
waterbome disease incidence;
discuss how these studies fit into the larger public policy framework on
providing safe drinking water: .
discuss planned and ongoing epidemiological studies and EPA/CDC activities
related to these mandates;
identify data gaps, research needs, and opportunities for improved
methodologies; and %
discuss next steps and opportunities for coordination and communication.
Thursday. October 9. 1997
8:30-8:45 Welcome, introductions, review agenda A.Amold, RESOLVE/
E.King, EPA
- Introductions
- Review meeting objectives, agenda, groundrules, and logistics
8:45-11:30 Overview on Background of Waterborne Disease Detection and
Federal Policy Development (Presentation and discussion)
3:45,9:30 " Statutory requirements and direction ofmicrobial drinking
water regulations and EPA/CDC Partnership, S. Regli, EPA ,
- Developing national waterbome disease estimates for drinking water
regulations, S. Regli, EPA
9 30-10.03 Detection of waterbome disease (endemic and epidemic) and
inherent difficulties and limitations, D. Juranek, CDC
io:os-io:2s Break
-------
Friday. October LO. 1997
9:00-10:45 'Approaches Towards A National Estimate, (breakout group report and
plenary discussion). (Each breakout group will report out the Thursday day afternoon
answer} to the four questions and then the plenary group will discuss the four questions),
Are there other potentially viable approaches that ought to be
considered in developing a national estimate?
Are there additional studies that ought to be considered to develop
a national estimate?
Are there other current and relevant techniques that ought to be
considered?
While developing a national estimate, what additional questions
about microbial contamination of drinking \vater and public health
need to be answered to most effectively protect public health?
i-
10:45-11:00 Break
11:00-12:30 Next Steps
- Workshop highlights and identification of unresolved questions
- Are there any technical, coordination, or other issues that ought to be
raised?
- Report on AWWARF 1998 Workshop, E. Lomaquahu. AWWARF
- Closing comments
12:30 p.m. Adjourn
-------
Attachment H
PARTICIPANT LIST
Environmental Protection Agency
and
Center for Disease Control
WATERBORNE DISEASE WORKSHOP
October 9 and 10, 1997
-------
Waterborne Disease^prkshop, Oct. 9-10,1997
PARTICIPANT LIST
lisa
Arthur
LonnJe
Philip
Susan
Valerie
Tom
Tracy
Brenda
Lynn
Rebecca I.
David
Keith
jjack
Peter t.
GuDther
John
Cora
Steve
Laura
Mary Ann
Aimodon
Ashendortf
Backer
Berger
Binder
Blank
Bonacqulsti
Bone
Boutin
Bradley
Calderon
Casemora
Christman
Coltord
Cook
Craun
Cromwell
Dones
Edberg
filers
Felge
6tu6STiHECD(«04J
Naw York City Department of
Environmental Protection
NCEH
US EPA
DPD/NCID/CDC,MSF22
USEPA08WDW
Fairfax County Water Authority
DS EPA (MC 4607)
0.8. EPA- (NCSA CIN)
Association of State and
Territorial PnbUc Health
Laboratory Directors
O.S. EPA, Epidemiology and
Blomarkers Branch
Pnbne Health Lsb.f PHIS
Cryptospordlnm Reference Unit
Chlorine Chemistry Council
School of Public Health
NAWC
Gunther Craon and Associates
Ipogee Research, Inc.
WSSC
Tale University School of
Medicine
ladonal Research
DSEPA
,4biM stmt, sw"
59-17 Junction Boulevard
4770 Bnford Hwy. NE
401 M Street SW
4770 Bnford Highway. NE
40IM Street SW
8560 Arlington Blvd.
40 1M Street. SW
Z6 W.Martin Lather Ring
Drive
1211 Connecticut Avenue,
NW
MD58A
Glan Ctwrde District
General B&spttal
1300 Wilson Boulevard
DC Berkeley
1725 K Street, NW
101 West Fredrick Street
4350 East West Highway
RLI, House 111
Department of Labor
Medicine
2101 Constitution Avenue,
NW
26 West Martin Luther
_ . .
3rd Floor Low Rise
MSF-46
Room 1219 ET
^ N
Waterside Mall
Suite 608
Rhyl Denblgshlre
140 Warren Bali
Suite 1212
Suite 104
Suite 600
Farmlngton Road
West
POBoi3333
Washington
Corona
Atlanta
Washington
Atlanta
Washington
Herri field
Washington
Cincinnati
Washington
Research
Triangle Park
Wales
Arlington
Berkeley
Washington
Sta union
Bethesda ,
Accokeek
lew Haven
Washington
^ncinnati
DC
NT
OA
DC
GA
DC
VA
DC
OH
DC
NC
₯A
CA
DC
VA
MD
MD
CT
DC
OH i
20460 "
11368
30341
20460
30341
20460
22I1B-
0815
20460
45268
20036
27711
U.18
5DJ
22209
94720
20006
24401
20814
20607
06510
20418
45268
202(260/1310
7181595-5340
7701488-7603
202(260-7006
770/488-7793
202(260-8387
703/698-5600
X476
202(260^2954
513569-7532
202(822-5227
919(9664617
0114411745-
583737
703(7415935
510/643^1076
202/8&8383
120
540/886-1939
301/6528444
301(206-7401
i
203(785-2457
202(3343*423
513/5697944 i
Page I
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Waterborne Disease Workshop, Oct. 9-10,1997
PARTICIPANT LIST
liltiffilJk^
Vernon
Mark
Steve
Emerson
Robin
Karl
Maureen
Jennifer
James R.
Christine
Robert D.
Tom
Diana
James V.
Erik
Steve
stig
Alan
Crystal C.
^{{^^fellMMMMMlllhlll^^^^^^^^^^^^^^^^H^^^H
Land
LeChevalller
Leonard
Lomaqnahn
Massengale
Maflan
McCJeiiand
McLaln
Miller
Moe
Morris
Navln
Neldie
O'Connor
Olson
Potts
Regii
Roberson
Rodgero
City of Norfolk Department of
tranutw
American Water Works Service
Co., Inc.
Jan Francisco PUC
AWWA Research Foundation
NAPWA
Lonls & Harrison
US EPA Region 1
USEPA-06WDW
NIC DepL of Health Parasitic
Disease SnneUance
bepi of Epidemiology
DepL of Family Medldne &
Commnnlty Health
CDC
Consumer Federation of America
An
Natural Resources Defense
Council
US EPA
US EPA Office of Groundwater
and DrtnMng Water
American Water Works
Association
US EPA
6040 Waterworks Road
i 025 Laural Oak Road
1155 Market Street
6668 West Qulncy Avenne
1413 K Street NW. Suite
700
ISCStreeiNW
JFK Federal Bldg.-(CCT)
40 IM Street, SW
125 Worth Street
School of Public Health
University of North
Carolina at Chapel Bill
Tufts University Medical
School ' * -v
4770 Buford Hwy
2129 Florida Ave.,MW
3102 Starner Court
1200 New Tork Avenue,
NW
OGWDW
.East Tower, Room 935D
1401 New Tort Avenne.
;NW
401 M Street SW East
Tower, Room 1113G
Division of Water
Production &
Quality
4th Floor
Sal te 740
Room 328, Boi 22A
CB 7400. McGavran
Greenberg Hall
138 Harrison Ave.
Mali Stop F n
Apt 401
401 M Street SW
401 M Street (4603).
SW
Suite 640
MC4607
Norfolk
Toorhees
San
Francisco
Denver
Washington
Washington
Boston
Washington
New York
Chapel Hill
Boston
Atlanta
Washington
Kensington
Washington
Washington
Washington
Washington
Washington
?A
NJ
CA
CO
DC
DC
MA
DC
NT
NC .
MA
GA
DC
MD~
DC
DC
DC
DC
DC
23502
OTO43
94103
50235
20005
20001
62203
20460
10013
27599-
7400
02111
30341
20008
20895
20005
20460
20460
20005
20460
757-44i5V78
imri&Ksi
41515540792
303/3474114
202/m04i4
202/39^3903
61756i3543
202^60^0431
212^8^9638
919/968-1420
617/838-1374
770/488-7766
202/667-9280
202/289-2360
202/2605015
202/260-7379
202/628-8303
.202/2604676
Page 3
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