Diarrhoeal diseases kill an estimated 2.5 million people each year, the majority of which are children under five years of age (Kosek 2003). An estimated four billion cases each year account for 5.7% of the global burden of disease and place diarrhoeal disease as the third highest cause of morbidity and sixth highest cause of mortality (Pruess 2002). Among children under five years in developing countries, diarrhoeal disease accounts for 21% of all deaths (Parashar 2003). By inhibiting normal consumption of foods and adsorption of nutrients, diarrhoeal diseases are also an important cause of malnutrition, which leads to impaired physical growth (Guerrant 1999), reduced resistance to infection (Baqui 1993), and potentially long-term gastrointestinal disorders (Schneider 1978).
The infectious agents associated with diarrhoeal disease are transmitted chiefly through the faecal-oral route (Byers 2001). A wide variety of bacterial, viral, and protozoan pathogens excreted in the faeces of humans and animals are known to cause diarrhoea. Many of these are potentially waterborne − transmitted through the ingestion of contaminated water (Leclerc 2002). Accordingly, a number of interventions have been developed to treat water. These include physical removal of pathogens (eg filtration, adsorption, and sedimentation), chemical treatment (eg assisted sedimentation, chemical disinfection, and ion exchange), or heat and ultra-violet (UV) radiation. Because of the risk of recontamination (Clasen 2003), interventions to improve water quality also include steps to maintain the microbiological quality of safe drinking water, such as piped distribution, residual disinfection, and improved storage. These efforts are expected to receive additional priority as a result of the United Nation's commitment to reduce by one half the 1.5 billion people without sustainable access to improved water (one of the United Nation's Millennium Development Goals) (United Nations 2000), and by the World Health Organization's steps to accelerate the health gains of safe water to the remaining population by improved treatment and storage of water at the household level (Sobsey 2002).
While water quality is also adversely impacted by chemical contaminants, the level of disease associated with metals, nitrates, organics and other chemicals is small relative to diarrhoea (WHO 2002). Other important diseases associated with drinking water, such as hepatitis A and E, poliomyelitis, gastroenteritis and typhoid fever, may not cause diarrhoea, but are nevertheless associated with waterborne microbes of faecal origin. For this reason, efforts to assess drinking water quality focus primarily on faecal pathogens (WHO 1993). Because of the difficulty of monitoring water for the presence of all such agents, an indirect approach has been adopted where water is examined for indicator bacteria whose presence implies some degree of contamination. While there is controversy over the preferred indicator (Gleeson 1997), even those that accept the use of the coliform group use different approaches to the indicator in studies (total coliforms, thermotolerant coliforms, Escherichia coli) and different methods for assaying the level of indicator present (membrane filtration, multiple tube/most probable number) (Clesceri 1998).
In higher income countries, and in many urban settings worldwide, drinking water is treated centrally and distributed through a system of pipes directly to household taps. In such settings, the principal risk of waterborne disease is from outbreaks often associated with a failure of the treatment or distribution system. Health authorities generally accept that microbiologically safe water plays an important role in preventing such outbreaks (Hunter 1997). Accordingly, the most widely accepted standard for water quality allows no detectable level of harmful pathogens at the point of distribution (WHO 1993). In settings that are not served by reliable water treatment and distribution systems, diarrhoeal disease is often endemic, that is, present or usually prevalent in the population at all times. However, in such settings much of the epidemiological evidence for increased health benefits following improvements in the quality of drinking water has been equivocal (Cairncross 1989; Esrey 1986; Lindskog 1987). Since many of these same waterborne pathogens are also transmitted via ingestion of contaminated food and other beverages, by person-to-person contact, and by direct or indirect contact with infected faeces, improvements in water quality alone may not necessarily interrupt transmission (Briscoe 1984).
Because of this variety of risk factors, interventions for the prevention of diarrhoeal disease not only include enhanced water quality but also steps to improve the proper disposal of human faeces (sanitation), increase the quantity and improve access to water (water supply), and promote hand washing and other hygiene practices within domestic and community settings (hygiene). As in the case of studies of water quality, there is a wide range in the reported measure of effect of these other environmental interventions on diarrhoea morbidity (Esrey 1985). Even more fundamentally, there are also questions about the methods and validity of studies designed to assess the health impact of such interventions (Briscoe 1986; Imo State Team 1989).
As part of a larger evaluation of interventions for the control of diarrhoeal disease (Feachem 1983), Esrey and colleagues reviewed previous studies to determine the health impact from improvements in water supplies and excreta disposal facilities (Esrey 1985). In 1991, the review was updated and expanded to cover studies addressing a variety of specific pathogens associated with poor water and sanitation (Esrey 1991). For almost two decades, these reviews have provided guidance on the relative reduction in diarrhoeal disease that was believed to be possible through improvements in water, sanitation and hygiene. However, a number of questions have been raised about the validity of these reviews.
First, while substantial progress has been made in reducing the mortality associated with diarrhoeal disease, morbidity remains essentially unchanged (Kosek 2003). One interpretation is that this suggests the success of interventions to improve case management, such as oral rehydration therapy and host resistance, but less success in reducing transmission of the pathogenic agents through the recommended environmental initiatives (Huttly 1997). Though this is, at best, indirect evidence, it should nevertheless give pause to those who seek to reduce diarrhoeal disease through environmental interventions.
Second, Esrey and colleagues based their conclusions chiefly on observational studies. In addition to the confounding and bias inherent in such studies, they and others have pointed out significant and widespread methodological problems with these studies (Blum 1983; Esrey 1986). A number of recent interventional studies, many of them randomized and controlled to minimize confounding and bias, have demonstrated a significantly larger reduction in diarrhoeal morbidity from interventions that primarily or exclusively improved drinking water quality (Mintz 2001).
Third, although these previous reviews were helpful in identifying the broad questions and suggesting answers, they did not employ the more rigorous methodologies and statistical methods, including meta-analysis, of a systematic review (Egger 2001). In terms of coverage, for example, neither review involved a comprehensive search strategy. Accordingly, the conclusions with respect to water quality are based on a very limited number of studies. The reviews were also limited to studies in the English language. With respect to statistical methods, the simple use of the median reduction in morbidity (the value at the midpoint of the distribution of study results) does minimize the effect of the extremes, as Esrey intended (Esrey 1991). However, it fails to take into account the size of the study and the variance observed in the results, factors that are weighted in meta-analysis to arrive at a pooled measure of effect (Deeks 2001). Moreover, it does not distinguish between the various case definitions (Moy 1991) and measures of diarrhoea morbidity (Morris 1996; Pickering 1987). In addition, while Esrey attempted to incorporate quality criteria in the reviews, there was no independent assessment of study quality or, for that matter, whether identified studies met the inclusion criteria. Furthermore, these prior reviews did not explore publication bias or conduct sensitivity analyses to assess the robustness of the findings.
Finally, and perhaps most significantly, while Esrey's league tables comparing the relative impact of various types of environmental interventions are enticingly simple, they fail to explain the potentially more important reasons for the broad differences within each type. In the case of water quality improvements, for example, Esrey cited a median reduction in diarrhoea disease from 9 studies of 16%, with a range in effect from 0% to 90%. Studies have demonstrated significant differences in diarrhoea morbidity arising from varying case definitions, recall periods for reporting episodes, reported versus clinically confirmed cases, age, seasonality, ambient level of contamination, and pathogenicity of the causative agents (Byers 2001). Subgroup analyses, such as the type of intervention described above, the point at which it is applied (eg point of supply versus point of use), and whether or not the intervention includes components in addition to improved water quality (eg sanitation, hygiene promotion, improved supply, safe storage) may also be important (Mintz 2001). By examining the reasons for the heterogeneity in the observed effect −a primary objective in systematic reviews − and by conducting such subgroup analyses, one can better predict the true effect that can be expected under the vastly different contextual circumstances presented in a particular disease setting from the type of intervention employed (Petitti 2000).
To assess interventions to improve the microbiological quality of drinking water on preventing diarrhoea among children and adults.
Criteria for considering studies for this review
Types of studies
Randomized and quasi-randomized controlled trials. The unit of randomization may include individuals, families, households, communities, or other clusters.
A quasi-randomized controlled trial is where the intervention is allocated in a way that is not truly random; for example, allocation by date of birth, day of the week, medical record number, month of the year, or the order in which participants are included in the study (eg alternation).
Types of participants
Children and adults, families, households, and communities from areas where diarrhoeal disease is endemic.
Types of intervention
Interventions aimed at improving the microbiological quality of drinking water, including steps to improve water quality by removing or deactivating microbiological pathogens (eg by filtration, sedimentation, chemical treatment, heat, or UV radiation) and protecting the microbiological integrity of water prior to consumption (eg by residual disinfection, protected distribution, or improved storage).
An intervention that has shown elsewhere to reduce the quantity or pathogenicity of waterborne microbes will be deemed, for purposes of the review, as an intervention to improve water quality, even if the particular study did not record such an improvement by microbiological examination. We will include interventions that combine improvements in water quality with other components such as improvements in water quantity or access, sanitation or hygiene, but will analyse these separately.
Excluded: studies of interventions designed to reduce diarrhoea through improvements in sanitation, hygiene, water quantity or water access, but which do not include a water quality improvement.
Participants who are following their usual practices with respect to drinking water rather than the prescribed intervention, or who receive a different type of intervention.
Types of outcome measures
- Diarrhoea episodes among individuals, whether or not confirmed by microbiological examination.
We will exclude trials that have no clinical outcomes; for example, trials that only report on microbiological pathogens in the stool.
- Mortality attributed to diarrhoea.
- Level of pre- and post- intervention faecal contamination of water.
- Utilization of intervention.
- Adverse events.
Search methods for identification of studies
See: Cochrane Infectious Diseases Group methods used in reviews.
We will attempt to identify all relevant studies regardless of language or publication status (published, unpublished, in press, and in progress).
We will search the following databases using the search terms and strategy described in Table 01.
- Cochrane Infectious Diseases Group's trials register (December 2003).
- Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library (Issue 4, 2003).
- MEDLINE (1966 to December 2003).
- EMBASE (1974 to December 2003).
- LILACS (1982 to 1982 to December 2003).
We will search the following conference proceedings of the following organizations for relevant abstracts: International Water Association (IWA) and Water, Engineering and Development Centre, Loughborough University, UK (WEDC).
Researchers, organizations, and pharmaceutical companies
We will contact individual researchers working in the field, organizations including Water, Sanitation and Health Programme of the World Health Organization; World Bank Water and Sanitation Program; UNICEF Water, Environment and Sanitation (WES); Environmental Health Project (EHP); IRC International Water and Sanitation Centre; Foodborne and Diarrheal Diseases Branch, Division of Bacterial and Mycotics Diseases, Centers for Disease Control and Prevention (CDC); US Agency for International Development (USAID); and the Department for International Development (DFID), UK for unpublished and ongoing trials.
We will also check the reference lists of all studies identified by the above methods.
Methods of the review
Selection of studies
Thomas Clasen (TC) and Tamer Rabie (TR) will independently review the titles and abstracts resulting from the searches and select all studies that potentially fall within the inclusion criteria for the review. After obtaining full copies of all such studies, we will independently determine if the trial meets such inclusion criteria. Where we agree, we will either include or exclude the trial. Where we are unable to agree, we will consult Sandy Cairncross (SC) who will make the final decision. Any studies that TC or TR proposed to include but which were ultimately determined by SC not to be included will be identified together with the reason for exclusion in the 'Characteristics of excluded studies'.
Assessment of methodological quality
TC and TR will independently assess the methodological quality the trials using generation of allocation sequence, allocation concealment, blinding, and loss to follow up.
We will classify generation of allocation sequence − the process used to generate the randomization list − as adequate if the method used is described and the resulting sequences are unpredictable (eg computer-generated random numbers, table or random numbers, coin toss, drawing lots); unclear if stated that the trial is randomized, but the method is not described; or inadequate if sequences could be related to outcomes (eg according to case record number, date of birth, alternation).
We will classify allocation concealment − the process used to prevent foreknowledge of group assignment − as adequate if the participants and the investigators enrolling participants cannot foresee assignment; unclear if method is not described; or inadequate if participants and investigators enrolling participant can foresee upcoming assignment.
We will classify blinding − whether the participant or outcome assessor is blind to the intervention group − as double blind if the trial uses a placebo or double dummy technique such that neither the participant or the assessor knows whether or not participant receives the intervention; single blind if the participant or the assessor knows whether or not participant receives the intervention; or open if both participant and assessor knows whether or not participant receives the intervention.
We will classify loss to follow up − the portion of participants in the trial who are not included in the analysis − as adequate if more than 90% of all participants randomized to the trial were included in the analysis; unclear if not clear what portion of participants randomized to the trial were included in the analysis; or inadequate if less than 90% of all participants randomized to the trial were included in the analysis.
Additionally, we will assess quasi-randomized controlled trials using the following criteria.
(1) Comparability of characteristics between intervention and control groups with respect to relevant baseline characteristics such as water quality, diarrhoeal morbidity, age, socioeconomic status, access to water, hygiene practices, and sanitation facilities. We will classify this as adequate if no substantial differences are present; unclear if not reported or not known if substantial differences exist; or inadequate if one or more substantial difference exists.
(2) Data collection for intervention and control groups at the same time. We will classify this as adequate if data collected at similar points in time; unclear if not reported or not clear from trial; or inadequate if data not collected at similar points in time.
Where we disagree on trial methodological quality, we will consult Ian Roberts who will make the final decision.
We will perform sensitivity analyses on the relevant subgroups in each category where there are sufficient studies.
TC will use a pre-piloted form to extract and record the data described in Table 02, and attempt to contact authors to supply missing data. We will record morbidity based on the measure used in the trial, but where possible will recalculate morbidity based on the available data. TC will enter the extracted data into Review Manager 4.2.
We will compile and analyse data using Review Manager 4.2. Using 95% confidence intervals, we will use weighted mean differences for continuous data and relative risk for binary data, and present the results for each trial in a table together with other relevant data.
We will analyse studies that randomize at a cluster level and do not statistically adjust for the smaller confidence intervals associated therewith separately from studies that randomize at the individual level or studies that do adjust for clustering.
We will perform tests for homogeneity by visually examining the forest plots and by using chi-squared test for heterogeneity using a 10% level of statistical significance. We anticipate heterogeneity, and will perform subgroup analyses based on the following criteria: type of water quality intervention; simple versus combined interventions (ie with hygiene message, improved supply, improved sanitation, safe storage); whether or not water quality is protected to point of use (ie by pipe, residual disinfection, or safe storage); self-reported, observed, or clinically confirmed cases; low (< 100 thermotolerant coliforms (TTC)/100 ml), medium (100 to 1000 TTC/100 ml) and high (>1000 TTC/100 ml) untreated water faecal contamination; and < 5 versus ≥ 5 years of age.
Where appropriate to pool data and heterogeneity is detected, we will use the random effects model. We will generate a pooled measure of effect using a meta-analysis for all pooled studies and for the subgroups.
Finally, we will produce forest plots to explore the existence of publication bias, heterogeneity of results, and differences in methodological quality.
Potential conflict of interest
The research of Thomas Clasen is supported in part by First Water, Ltd., a private company that develops, distributes and evaluates point-of-use water treatment systems. Sandy Cairncross and Tamer Rabie participate in hygiene research supported by Unilever.
Sources of support
External sources of support
- No sources of support supplied
Internal sources of support
- No sources of support supplied