Program 1 Newsletter - Issue 5 - March 1997

New Research Project
Double blinded randomised controlled cross over trial on disinfection by products in
drinking water and micronucleated bladder epithelial cells

Cryptosporidium outbreak near London
Contact lens warning issued in UK
Canadian Drinking Water Materials Safety Act
New York Watershed Agreement
Epidemiology Spot
Disease measurement
News Items
From the Literature
Forthcoming meetings
Contact Information

New Research Project

Double blinded randomised controlled cross over trial on disinfection by products in drinking water and micronucleated bladder epithelial cells.
Project Leaders - Dr Louis Pilotto and Dr Geetha Ranmuthugala, NCEPH.

Since the discovery of its disinfection properties, chlorine has been used widely to disinfect community water supplies in industrially developed and developing countries. The discovery of disinfection by products (DBP) in the early 1970's caused much concern over the potential public health risks associated with these by products.

Although many epidemiological studies have been undertaken in an attempt to establish the causal link between DBP and drinking water, the evidence has not been convincing for several reasons. The long latency period associated with cancer development, the small relative risk over and above those drinking unchlorinated water, the difficulty in assessing confounders, and the difficulty in accurately measuring and quantifying exposure, are all contributory factors.

This prospective study will take a different approach to the problem - measuring and quantifying exposure at an individual level, and assaying the short-term affects of DBP on a biomarker of genotoxic damage. The chosen biomarker is the formation of micronuclei in bladder epithelial cells. Micronuclei are DNA fragments or whole chromosomes that are not incorporated into daughter cells during cell division. A number of different types of chromosomal aberrations including micronuclei are thought to be an initial step in carcinogenesis. It is therefore proposed that the effect of DBP on the frequency of micronucleated bladder epithelial cells will serve as an indicator of the potential carcinogenicity of DBP in drinking water.

This study will be conducted in Bungendore, NSW, where the community (tap) water supply is unchlorinated. The design is a double blinded randomised controlled cross over trial, involving 140 participants aged 45 to 65 years who will be recruited from the Electoral Roll. The participants will be randomly assigned to 2 groups, one group will be supplied with bottled unchlorinated water while the other will be supplied with bottled chlorinated water. Participants will be asked to drink at least 2 glasses of bottled water per day.

The frequency of micronuclei in bladder epithelial cells for each participant will be assessed from urine samples taken at baseline (before the bottled water is supplied) and intervals during a 5 week test period. There will be a 4 week wash out period when all participants will revert to drinking Bungedore tap water, then a further 5 week period with bottled water supply where the type of water supplied will be reversed (ie those who received chlorinated water during the first test period will receive unchlorinated water during the second period, and vice versa).

Current and recently quit smokers will be excluded from the study as smoking is known to increase the frequency of micronucleated cells. Anyone with a current diagnosis of malignancy will also be excluded. Water consumption will be assessed by questionnaire, and exposure to other sources of chlorinated water (eg drinking at workplace, swimming in chlorinated pools) will also be monitored.

This project has been funded by the CRCWQT and will also receive support from ACTEW in the conduct of laboratory analyses of water samples. The technique for detecting micronucleated cells (Fluorescein In Situ Hybridisation) has not previously been used for this purpose in Australia, and this method will be set up at the Australian National University and validated with assistance from experts at the University of California in Berkeley. Preliminary pilot work for the study has already begun, and the controlled trial will be conducted in the second half of this year.


Cryptosporidium outbreak near London

Up to 680,000 people in the region north east of London have been instructed to boil their drinking water due to Cryptosporidium contamination of the water supply. The warning was issued on Sunday 2nd March, following an emergency meeting of the Three Valleys Water Company, local health authorities, councils and national health experts. The affected area covers about 250 square miles (650 square kilometres) and extends from the northern outskirts of London to parts of Hertfordshire and Bedfordshire.

Public health officials had noted a 3-fold increase in laboratory confirmed diagnoses of cryptosporidiosis in the previous week, however routine tests for Cryptosporidium in the water supply were negative at this time. Further testing found oocysts in samples of finished water from two treatment plants on two consecutive days, prompting the emergency meeting and the decision to issue the boil water advisory.

By Wednesday 5th March, 38 cases had been confirmed with the majority reportedly occurring in children. Six schools in the area had closed and shops had reported panic buying of bottled water. A telephone helpline established by the water company to handle public inquiries was jammed with calls. Preliminary investigations by the Environment Agency failed to reveal any source of pollution that might have affected the underground water source.

Health officials estimate that about 5,000 cases of cryptosporidiosis occur each year in England and Wales, but it is not known what proportion of these arise from waterborne sources. The number of cases rises in spring and autumn, but the recent upsurge was higher than the seasonal average, alerting surveillance teams to the problem.

Some local councillors and politicians have called for legal action against the French-owned Three Valleys Water Company, critising the two day delay from the time of the first positive water test to issuing the warning. However the company has defended its actions, stating that it followed national guidelines in waiting for the results of repeat tests.

The issuing of a boil water notice was described as a “difficult decision” by the Director of Public Health for West Hertfordshire, Dr Barry Tennison. Such warnings carry the inherent risk of accidents from scalding and fires resulting from pots of water being allowed to boil dry, and these must be balanced against the risks of the apparent water contamination.

As of Thursday 20th March a total of 250 laboratory confirmed cases of cryptosporidiosis had occurred and several people had been hospitalised. The source of water contamination had still not been identified, and the boil water advisory remained in effect.

The publicity surrounding the outbreak extended to coverage of a speech given on 5th March by Prof Ian Aitken, retiring Director of the Moredun Research Institute near Edinburgh. The Institute carries out research on diseases of domestic animals and wildlife, including basic research on Cryptosporidium. The Institute’s current 3 year grant for the Cryptosporidium program is due to end this year, and may not be renewed.

Prof Aitken criticised government funding cutbacks which threatened long-term research programs, and described current practice as a “short-term, stop-go, fire-brigade pattern of scientific funding”. He commented that funds were being redirected to each health crisis as it arose - for example BSE (mad cow disease), E.coli 0157 food poisoning or whatever else “hits the headlines” rather than providing support for long-term studies.

The neglect of public health and health promotion by successive governments is also being targeted by the British Medical Association. The Chairman of the BMA, Dr Sandy Macara, recently described the state of public health in Britain as “slipping back into the last century” and warned that even standards of basic hygiene are declining. The BMA plans to lobby all political parties in the pending British election to adopt its six-point plan covering a range of health issues.


Contact lens warning issued in UK

The British Department of Health issued a warning on 13th February 1997 that wearers of contact lens should avoid washing lens storage containers in tap water. A report in the Daily Telegraph on 14th February quoted ophthalmologist Dr David Seal as saying that research had shown tap water to be the source of infection in 30 people suffering from acanthamoeba keratitis - an inflammation of the eye surface caused by infection by an amoeba.

The problem is linked to growth of the micro-organism in the storage container, and wearers have been advised to use only purchased sterile solutions or boiled water (cooled to 70ºC) for washing the containers. Acanthamoeba are common in tap water and like some other protozoa they can form cysts which are resistant to many disinfectants including chlorine.

The corneal infections produced by this micro-organism can lead to permanent damage and loss of vision if not quickly diagnosed and correctly treated. Corneal grafting may be required in severe cases. The infection may be complicated by the presence of a variety of pathogenic bacteria which are ingested by the amoeba. These bacteria may survive inside the amoeba and can be released onto the eye surface under the contact lens. The entrapment of micro-organisms under the contact lens probably favours their growth, and may provide a degree of protection from the action of protective enzymes and antibodies in tears.

No infection problems have been attributed to incidental eye contact with tap water during showering or swimming, as the natural defence mechanisms of the eye can eliminate small numbers of micro-organisms.


Canadian Drinking Water Materials Safety Act

The Canadian Government has introduced a new Act of Parliament governing the sale and import of drinking water materials. The Drinking Water Materials Safety Act will regulate all materials that come into contact with drinking water including treatment chemicals, treatment devices (eg home water filters and jugs) and system components (eg municipal and household pipes, pumps, tanks and taps). The legislation will also cover advertising and promotional claims, and will govern product labelling and maintenance instructions provided to consumers.

At present about 30% of components and devices sold in Canada are certified under US based standards, but the remainder are of unknown quality and performance characteristics in terms of health effects. The new legislation will be phased in over a 2 to 5 year period, and will provide enforceable nationwide standards.

The legislation has been developed in consultation with public health workers, industry associations and professional associations. The aim was to formulate effective ways of protecting public health without placing an unnecessary financial or administrative burden on industry.

Certification of products will be carried out by third-party organisations accredited by the Standards Council of Canada, and the consultation process with stakeholders will continue as the provisions of the Act are put in place.

Comment: In Australia, senior figures in the water industry have expressed concern that the recent corporatisation of water authorities has led to gaps in the responsibility for regulation of domestic plumbing materials in some states. This may lead to situations where water quality at the consumer’s tap is adversely affected by inferior household fittings beyond the control of water utilities. Some form of national regulation of drinking water plumbing materials is seen by many as desirable to safeguard public health.


New York Watershed Agreement

The US EPA has given approval to New York City to pursue a program of reservoir protection and sewerage plant upgrades to improve drinking water quality rather than forcing the city to build a filtration plant. Under the agreement, New York will have at least until the year 2002 to implement water quality improvements before the EPA will reconsider the question of filtration.

Approximately 90% of New York’s drinking water comes from surface catchments to the north of the city, and it is the only US city with a population over 1 million which does not filter its drinking water. About 9 million residents of the city and outlying suburbs are served by this water supply, but the city owns less than 10% of the 1,900 square mile (4900 square kilometre) catchment area.

The catchment in the Catskill / Delaware mountains has a permanent population of 77,000 people and is a popular summer resort destination. There is also a substantial farming industry with about 350 farms (mainly dairy) in the catchment.

The New York City Watershed Agreement includes a 5 year US$660 million program to upgrade more than 100 old sewage plants and introduce other measures to reduce the pollution of the watershed. The program will include an extensive overhaul of outdated regulations governing development and sanitation facilities for the area, and the city will purchase some privately owned landholdings.

According to a report in the New York Times of 22nd January the agreement between city, state and federal officials and a coalition of small communities from the watershed was the product of 21 months of negotiations. The prolonged discussions appear to have led to a high level of satisfaction with the new working arrangements from both environmental groups and community representatives. The cost of the improvement program is expected to add about US$35 to the average US$400 annual water bill of New York residents by the year 2002.

The city will also be required to complete the design plans for a filtration system as a contingency measure in the event that the catchment upgrade program is not able to satisfy the EPA requirements. If the system is eventually built it would need to be the largest in the world with a capacity of more than a billion gallons (3.8 billion litres) per day. The probable capital cost would be of the order of US$8 billion.


Epidemiology Spot

Disease Measurement
An important part of epidemiology is estimating the frequency and distribution of a disease in the population and examining the effect of suspected risk factors.

Measuring Disease Frequency: Measures of disease frequency help us to describe how common (or uncommon) an illness (or other outcome event) is in the population at risk. The frequency of cases (or outcomes) is measured in relation to population and time.

There are two main types of measures of disease frequency - prevalence and incidence. Incidence is the number of new cases occurring in a given time period and prevalence is the total number of cases at a given point in time.

Prevalence: Prevalence is the proportion of people in a defined population, who have the outcome under study at a defined instant (a point) in time. For example:

Incidence: Incidence measures are concerned with the frequency of new cases. For example: There are two measures of incidence - risk and rate. For rare outcomes these can be numerically similar.
Risk - is the probability that a disease will occur in a disease free population, during a specified time period. To calculate the risk we divide the number of new cases in the defined period by the population initially at risk.

risk (over a defined period) = new cases / population at risk

Risk is a probability and therefore cannot be more than 1 or 100%. It is usually applied to the first episode of a particular disease.

Rate - measures the frequency of appearance of new cases and relates them to the “person-time” at risk. This measure takes into account changes in the population at risk during the follow-up period and is usually defined as “person-years at risk” or “person-days at risk”.

rate = the number of new cases / person-years at risk

Risk and rate have the same numerator (the number of new cases) but different denominators.
Risk relates the number of new cases during a time period to the population at risk at the beginning of the period.
Rate relates the number of new cases to a more precise measure of the population at risk during the study period. This is because the population under study may change throughout the study period due disease, death, migration or dropping out of the study.
The denominator in rate ie. “person-years at risk” is the sum of the time each person in the study population remained at risk of developing the outcome during the study period.

The difference between risk and rate can be illustrated by considering a hypothetical example of cases of gastroenteritis due to a specific micro-organism arising in a population of 600 people observed over 1 year. In this example we have assumed that once a person is infected they develop immunity and are therefore no longer at risk.

Month		Population	Number of
		at risk		new cases
Jan		600		5	
Feb		595		5
Mar		590		5
Apr		585		5
May		580		5
Jun		575		5
Jul		570		5
Aug		565		5
Sep		560		5
Oct		555		5
Nov		550		5
Dec		545		5

For this population the risk of gastroenteritis is 60 /600 people per year or 0.1000 per year. However the rate of gastroenteritis is 60 /572.5 person-years at risk or 0.1048 per person-year.

Issues in calculating measures of frequency:

1) The population at risk: It is very important to define who is the population at risk and to state this very clearly. If a person is not at risk of the disease they should not be counted in the population at risk. For example when assessing the risk of developing prostate cancer, women should not be counted in the population at risk because the do not have a prostate gland and could not possibly develop prostate cancer.

2) Choosing between rate and risk: In the majority of situations there is little change in the population at risk of a disease particularly if the disease is rare - in which case the rate and the risk over a period of unit time are similar.

3) Defining a Case: It is important to have a standard definition of what constitutes a case so that measures of the frequency of disease are comparable.

This definition should take into account -
The severity of the disease. Disease severity is important when assessing the effectiveness of medication. An example is measuring the effectiveness of an antibiotic if an individual has gastroenteritis. The effect of the antibiotic and its ability to cure the patient may be dependant on whether the person has mild disease versus severe disease.

Whether all episodes are counted or just the first time an illness (or outcome) is diagnosed. Do you measure when a person has their first stroke or every time an individual has a stroke, when assessing the rate of strokes in a community?

Whether organs affected or people affected are counted. When measuring cataract do you measure the number of people who have cataract(s) or the number of eyes which are affected by cataract? This is important as none, one or both eyes may be affected.

Case definitions may vary from one study to another - thus it is important to clearly state the case definition so that limitations in comparability between studies are evident.


News Items

DHS VIC to join CRCWQT
The Department of Human Services Victoria will shortly become a partner in the CRCWQT. The DHS has played an active role in the development of the Program 1 research agenda, and is one of several organisations funding the Water Quality Study. The resolution to admit the DHS as a partner was passed at the CRCWQT Board of Management meeting on 9th December 1996.

Industry Liaison Officer appointed
Dr Gerard Vaughan has been appointed as the Industry Liaison Officer for the CRCWQT. Dr Vaughan served as a member of the Victorian Legislative assembly for 1979 to 1996. Prior to entering politics, he worked as a research scientist with CSIRO and has a background in Chemical Engineering with experience in water research.

Public Health Priorities in Managing Drinking Water - Workshop Proceedings
The proceedings of the joint WSAA-CRCWQT workshop held in Melbourne in September 1996 have been published as the first in a series of Occasional Papers by the CRCWQT. About 350 copies of the publication have been distributed to WSAA members and those on the CRCWQT mailing list. Anyone else seeking a copy should contact Mr George Turelli, CRCWQT (Fax 08 8259 0228).

Aluminium Report published
The report Biological Aspects of Aluminium in Food and Water Supply by Dr Fiona Cummings is now available from the Urban Water Research Association of Victoria (Report 201, via the AWWA Bookshop - Phone 02 9413 1288).

ICR implementation delayed
It was reported in the February edition of the Journal of the American Water Works Association that the implementation of the data collection phase of the Information Collection Rule (ICR) will be postponed by several months. Delays have occurred due to the time required for laboratory approvals by the EPA, and need for up to three quarters of water utilities to revise their initial sampling plans to suit the EPA data system. Monitoring for viral, protozoan and chemical contaminants is likely to start mid-year rather than in February as planned.

AWWA court action dropped
The US AWWA has dropped its court challenge to the EPA’s ICR legislation. The EPA has agreed that either the AWWA or individual water utilities will retain the right of legal challenge to the legislation in the future. The withdrawal of litigation cleared the way for open discussions to resume between stakeholders and the EPA.

Acceptable microbial risk questioned
Charles Haas, Professor of Environmental Engineering at Drexel University, Philadelphia and a leading author on risk assessment has questioned the current concept that the acceptable microbial risk for water supplies should be set at 1 infection per 10,000 people per year. In the “Viewpoint” article in the December 1996 issue of the Journal of the US AWWA, Prof Haas pointed out that this figure was derived in the 1980s and appeared to be based on the estimated risk of illness from recognised waterborne outbreaks in developed countries at that time.

It is now believed that recognised outbreaks constitute only a minor portion of waterborne disease, and in continuing to apply this figure for acceptable risk we have in fact moved the goal posts by several orders of magnitude. Prof Haas advocates urgent reconsideration of the acceptable risk level in the light of changing evidence.

US National Water Program Agenda
The US has marked the 25th Anniversary of the 1972 Clean Water act by releasing a National Water Program Agenda for 1997/98. The program includes an Operating Framework, Water Program Priority Areas and the Management Sytem - Promoting Flexibility with Accountability. The Agenda is intended to assist in communicating water program goals and priorities to the public and the water community, and to provide a management tool with program directions and a basis for assessment.

$12 billion needed for US water improvements
A survey of drinking water utilities carried out by the US EPA has shown that communities need more than US$ 12 billion in the immediate future to protect public drinking water supplies. The detailed survey of 4,000 representative communities was used to estimate the needs of the 55,000 water systems that serve communities in the United States.
An EPA press release on 31st January reported that more than 80% of the funds required in the immediate future were needed to improve the microbiological safety of water supplies. The remaining funds were needed to protect water supplies from lead, nitrate and other chemical contaminants. The nationwide survey also asked water utilities about their long term needs for the replacement and refurbishment of drinking water infrastructure. The responses indicated a total requirement of more than US$ 138 billion over the next 20 years.

When does water become wet?
An article in the 7th February issue of Science described the work of theoretical chemists Jon Gregory and David Clary in computer modelling the interactions of water molecules. Their work has led to the conclusion that a minimum of six water molecules are required to hold another molecule in solution. Smaller numbers of water molecules are able to associate by hydrogen bonding into flat ring structures but six water molecules are able to form a three dimensional “cage” to enclose the solute molecule.
Gregory JK, Clary DC et al. (1997). The water dipole moments in water clusters. Science 275 p814-817.

Wine safer than water?
The recent outbreak of Cryptosporidium near London prompted French chef Jean Conil, president of the Epicurean World Master Chefs Society to pronounce it is “safer to drink wine than British water”. The Daily Telegraph’s cookery writer Thane Prince retorted that “you can’t make a decent cup of tea out of French water”.

England faces another drought
Record low rainfall over the last 9 months has left most of southern England facing possible water shortages. Rainfall in the catchment area of Thames Water was 31% of normal in December 1996 and 17% of normal in January 1997, leaving groundwater levels well below average for the time of year. A number of UK water supply companies are mounting campaigns to encourage customers save water, including offering to supply free of charge devices for toilet cisterns to reduce flush volumes.


From the Literature


Forthcoming Meetings

Management Committee Meeting
The next meeting of the Management Committee of the CRCWQT will take place on 28th April in Canberra, and will be hosted by NCEPH.

Board of Management
The next meeting of the Board of Management of the CRCWQT will take place on 23rd June in Brisbane.


Contact Information
Editor - Martha Sinclair email martha.sinclair@med.monash.edu.au
Assistant Editor - Pam Lightbody email pam.lightbody@med.monash.edu.au

The printed version of Health Stream is available free of charge - to be added to our mailing list please contact Pam Lightbody (email above or fax + 61 3 9903 0576).