A re-assessment of the safety of silver in household water treatment: rapid systematic review of mammalian in vivo genotoxicity studies.

BACKGROUND: Despite poor evidence of their effectiveness, colloidal silver and silver nanoparticles are increasingly being promoted for treating potentially contaminated drinking water in low income countries. Recently, however, concerns have been raised about the possible genotoxicity of particulate silver. OBJECTIVES: The goal of this paper was to review the published mammalian in vivo genotoxicity studies using silver micro and nanoparticles. METHODS: SCOPUS and Medline were searched using the following search string: ("DNA damage" OR genotox* OR Cytotox* OR Embryotox*) AND (silver OR AgNP). Included papers were any mammalian in vivo experimental studies investigating genotoxicity of silver particles. Studies were quality assessed using the ToxRTool. RESULTS: 16 relevant papers were identified. There were substantial variations in study design including the size of silver particles, animal species, target organs, silver dose, route of administration and the method used to detect genotoxicity. Thus, it was not possible to produce a definitive pooled result. Nevertheless, most studies showed evidence of genotoxicity unless using very low doses. We also identified one human study reporting evidence of "severe DNA damage" in silver jewellery workers occupationally exposed to silver particles. CONCLUSIONS: With the available evidence it is not possible to be definitive about risks to human health from oral exposure to silver particulates. However, the balance of evidence suggests that there should be concerns especially when considering the evidence from jewellery workers. There is an urgent need to determine whether people exposed to particulate silver as part of drinking water treatment have evidence of DNA damage.

Recreational Water and Infection: A Review of Recent Findings.

This paper reviews the latest evidence provided by epidemiological studies and quantitative microbial risk assessments (QMRAs) of infection risk from recreational water use. Studies for review were selected following a PubMed search for articles published between January 2010 and April 2014. Epidemiological studies show a generally elevated risk of gastrointestinal illness in bathers compared to non-bathers but often no clear association with water quality as measured by faecal indicator bacteria; this is especially true where study sites are impacted by non-point source pollution. Evidence from QMRAs support the lack of a consistent water quality association for non-point source-impacted beaches. It is suggested that source attribution, through quantified microbial source apportionment, linked with appropriate use of microbial source tracking methods should be employed as an integral part of future epidemiological surveys.

Hygiene and health: systematic review of handwashing practices worldwide and update of health effects.

OBJECTIVE: To estimate the global prevalence of handwashing with soap and derive a pooled estimate of the effect of hygiene on diarrhoeal diseases, based on a systematic search of the literature. METHODS: Studies with data on observed rates of handwashing with soap published between 1990 and August 2013 were identified from a systematic search of PubMed, Embase and ISI Web of Knowledge. A separate search was conducted for studies on the effect of hygiene on diarrhoeal disease that included randomised controlled trials, quasi-randomised trials with control group, observational studies using matching techniques and observational studies with a control group where the intervention was well defined. The search used Cochrane Library, Global Health, BIOSIS, PubMed, and Embase databases supplemented with reference lists from previously published systematic reviews to identify studies published between 1970 and August 2013. Results were combined using multilevel modelling for handwashing prevalence and meta-regression for risk estimates. RESULTS: From the 42 studies reporting handwashing prevalence we estimate that approximately 19% of the world population washes hands with soap after contact with excreta (i.e. use of a sanitation facility or contact with children's excreta). Meta-regression of risk estimates suggests that handwashing reduces the risk of diarrhoeal disease by 40% (risk ratio 0.60, 95% CI 0.53-0.68); however, when we included an adjustment for unblinded studies, the effect estimate was reduced to 23% (risk ratio 0.77, 95% CI 0.32-1.86). CONCLUSIONS: Our results show that handwashing after contact with excreta is poorly practiced globally, despite the likely positive health benefits.

Assessing the impact of drinking water and sanitation on diarrhoeal disease in low- and middle-income settings: systematic review and meta-regression.

OBJECTIVE: To assess the impact of inadequate water and sanitation on diarrhoeal disease in low- and middle-income settings. METHODS: The search strategy used Cochrane Library, MEDLINE & PubMed, Global Health, Embase and BIOSIS supplemented by screening of reference lists from previously published systematic reviews, to identify studies reporting on interventions examining the effect of drinking water and sanitation improvements in low- and middle-income settings published between 1970 and May 2013. Studies including randomised controlled trials, quasi-randomised trials with control group, observational studies using matching techniques and observational studies with a control group where the intervention was well defined were eligible. Risk of bias was assessed using a modified Ottawa-Newcastle scale. Study results were combined using meta-analysis and meta-regression to derive overall and intervention-specific risk estimates. RESULTS: Of 6819 records identified for drinking water, 61 studies met the inclusion criteria, and of 12,515 records identified for sanitation, 11 studies were included. Overall, improvements in drinking water and sanitation were associated with decreased risks of diarrhoea. Specific improvements, such as the use of water filters, provision of high-quality piped water and sewer connections, were associated with greater reductions in diarrhoea compared with other interventions. CONCLUSIONS: The results show that inadequate water and sanitation are associated with considerable risks of diarrhoeal disease and that there are notable differences in illness reduction according to the type of improved water and sanitation implemented.

Burden of disease from inadequate water, sanitation and hygiene in low- and middle-income settings: a retrospective analysis of data from 145 countries.

OBJECTIVE: To estimate the burden of diarrhoeal diseases from exposure to inadequate water, sanitation and hand hygiene in low- and middle-income settings and provide an overview of the impact on other diseases. METHODS: For estimating the impact of water, sanitation and hygiene on diarrhoea, we selected exposure levels with both sufficient global exposure data and a matching exposure-risk relationship. Global exposure data were estimated for the year 2012, and risk estimates were taken from the most recent systematic analyses. We estimated attributable deaths and disability-adjusted life years (DALYs) by country, age and sex for inadequate water, sanitation and hand hygiene separately, and as a cluster of risk factors. Uncertainty estimates were computed on the basis of uncertainty surrounding exposure estimates and relative risks. RESULTS: In 2012, 502,000 diarrhoea deaths were estimated to be caused by inadequate drinking water and 280,000 deaths by inadequate sanitation. The most likely estimate of disease burden from inadequate hand hygiene amounts to 297,000 deaths. In total, 842,000 diarrhoea deaths are estimated to be caused by this cluster of risk factors, which amounts to 1.5% of the total disease burden and 58% of diarrhoeal diseases. In children under 5 years old, 361,000 deaths could be prevented, representing 5.5% of deaths in that age group. CONCLUSIONS: This estimate confirms the importance of improving water and sanitation in low- and middle-income settings for the prevention of diarrhoeal disease burden. It also underscores the need for better data on exposure and risk reductions that can be achieved with provision of reliable piped water, community sewage with treatment and hand hygiene.

An attempt to quantify the health impacts of flooding in the UK using an urban case study.

OBJECTIVES: To quantify, so far as possible, the health effects of flooding in the UK to allow comparison between different flooding events. METHODS: The health effects resulting from flooding events were determined through an extensive literature search, where information existed to enable the quantification of these effects. Disability-adjusted life years (DALYs) were used to enable the comparison between different health impacts and different flood events and populations, using two sites subject to pluvial flooding in the Bradford area, UK. RESULTS: Relatively few properties (and hence people) were affected by flooding in the case study areas and there were no predicted deaths or serious injuries; these results were supported by anecdotal knowledge of the events. Mental health problems, characterized as psychological distress, were estimated for adults; these were found to dominate the calculated health impacts, being considerably greater than the combined physical symptoms in the case study examples. CONCLUSIONS: While it was not possible to quantify every flood-related health impact, this method does allow comparisons to be made between different flood events and mitigation strategies.

An attempt to estimate the global burden of disease due to fluoride in drinking water.

A study was conducted to examine the feasibility of estimating the global burden of disease due to fluoride in drinking water. Skeletal fluorosis is a serious and debilitating disease which, with the exception of one area in China, is overwhelmingly due to the presence of elevated fluoride levels in drinking water. The global burden of disease due to fluoride in drinking water was estimated by combining exposure-response curves for dental and skeletal fluorosis (derived from published data) with model-derived predicted drinking water fluoride concentrations and an estimate of the percentage population exposed. There are few data with which to validate the output but given the current uncertainties in the data used, both to form the exposure-response curves and those resulting from the prediction of fluoride concentrations, it is felt that the estimate is unlikely to be precise. However, the exercise has identified a number of data gaps and useful research avenues, especially in relation to determining exposure, which could contribute to future estimates of this problem.

Reply to comments on "Derivation of numerical values for the World Health Organization guidelines for recreational waters".

The contribution addressed reveals an optimistic design philosophy likely to systematically underestimate risk in epidemiologic studies into the health effects of bathing water exposures. The authors seem to recommend that data on the 'exposure' measure (i.e. water quality) in such studies should be acquired in a similar manner to that used for regulatory sampling. This approach may compromise the quality of the epidemiologic investigations undertaken. It may result in imprecise estimates of exposure because it ignores the fact that regulatory timescales and spatial resolution (even if artificially compressed to a bathing day) can mask large spatial and temporal variability in water quality. If this variability is ignored by taking some mean value and attributing that to all of those exposed in a period at a study location, many bathers may be misclassified and the studies may be biased to a 'no-effect' conclusion. A more appropriate approach is to maximise the precision of the epidemiologic investigations by measurement of individual exposure (or water quality) at the place and time of the exposure, as has been done in randomised volunteer studies in the UK and Germany. The precise epidemiologic relationships linking 'exposure' with 'illness' can then be related to the probability of exposure to particular water quality by a 'normal bather' using the known probability distribution of the exposure variable (i.e. faecal indicator concentration) in the regulated bathing waters. We suggest that any research protocol where poor sampling design for water quality assessment is justified because regulatory monitoring is equally imprecise may be fundamentally flawed. The rationale for this assessment is that the epidemiology is the starting point and evidence-base for 'standards'. If precision is not maximised at this stage in the process it compromises the credibility of the standards design process. The negative effects of the approach advocated in this 'comment' are illustrated using published research findings used to derive the figures illustrated in Wymer et al. [2005. Comment on derivation of numerical values for the World Health Organization guidelines for recreational waters. Water Research 39, 2774-2777].

An estimation of the global burden of disease due to skin lesions caused by arsenic in drinking water.

The global burden of disease due to skin lesions caused by arsenic in drinking water was estimated by combining country-based exposure data with selected exposure-response relationships derived from the literature. Populations were considered to be exposed to elevated arsenic levels if their drinking water contained arsenic concentrations of 50 microg I(-1) or greater. Elevated arsenic concentrations in drinking water result in a significant global burden of disease, even when confining the health outcome to skin lesions. The burden of disease was particularly marked in the World Health Organization (WHO) comparative risk assessment (CRA) 'Sear D' region, which includes Bangladesh, India and Nepal. Unsurprisingly, Bangladesh was the worst affected country with 143 disability adjusted life years (DALYs) per 1,000 population. Although this initial estimate is subject to a large degree of uncertainty, it does represent an important first step in allowing the comparison of the problem relating to elevated arsenic in drinking water to other environmental health outcomes.

Water, sanitation, and hygiene interventions to reduce diarrhoea in less developed countries: a systematic review and meta-analysis.

Many studies have reported the results of interventions to reduce illness through improvements in drinking water, sanitation facilities, and hygiene practices in less developed countries. There has, however, been no formal systematic review and meta-analysis comparing the evidence of the relative effectiveness of these interventions. We developed a comprehensive search strategy designed to identify all peer-reviewed articles, in any language, that presented water, sanitation, or hygiene interventions. We examined only those articles with specific measurement of diarrhoea morbidity as a health outcome in non-outbreak conditions. We screened the titles and, where necessary, the abstracts of 2120 publications. 46 studies were judged to contain relevant evidence and were reviewed in detail. Data were extracted from these studies and pooled by meta-analysis to provide summary estimates of the effectiveness of each type of intervention. All of the interventions studied were found to reduce significantly the risks of diarrhoeal illness. Most of the interventions had a similar degree of impact on diarrhoeal illness, with the relative risk estimates from the overall meta-analyses ranging between 0.63 and 0.75. The results generally agree with those from previous reviews, but water quality interventions (point-of-use water treatment) were found to be more effective than previously thought, and multiple interventions (consisting of combined water, sanitation, and hygiene measures) were not more effective than interventions with a single focus. There is some evidence of publication bias in the findings from the hygiene and water treatment interventions.

Drinking-water nitrate, methemoglobinemia, and global burden of disease: a discussion.

On behalf of the World Health Organization (WHO), I have undertaken a series of literature-based investigations examining the global burden of disease related to a number of environmental risk factors associated with drinking water. In this article I outline the investigation of drinking-water nitrate concentration and methemoglobinemia. The exposure assessment was based on levels of nitrate in drinking water greater than the WHO guideline value of 50 mg/L. No exposure-response relationship, however, could be identified that related drinking-water nitrate level to methemoglobinemia. Indeed, although it has previously been accepted that consumption of drinking water high in nitrates causes methemoglobinemia in infants, it appears now that nitrate may be one of a number of co-factors that play a sometimes complex role in causing the disease. I conclude that, given the apparently low incidence of possible water-related methemoglobinemia, the complex nature of the role of nitrates, and that of individual behavior, it is currently inappropriate to attempt to link illness rates with drinking-water nitrate levels.

Derivation of numerical values for the World Health Organization guidelines for recreational waters.

In April 2001, draft 'Guidelines' for safe recreational water environments were developed at a World Health Organization (WHO) expert consultation. Later the same month, these were presented and discussed at the 'Green Week' in Brussels alongside the on-going revision of the European Union Bathing Water Directive 76/160/EEC. The WHO Guidelines cover general aspects of recreational water management as well as define water quality criteria for various hazards. For faecal pollution, these include faecal indicator organism concentrations and an assessment of vulnerability to faecal contamination. Central to the approach set out in the WHO Guidelines are: (i) the concept of beach profiling to produce a 'sanitary inspection category' which implies a priori hazard assessment as a core management tool and (ii) the prediction of poor water quality to assist in real time risk assessment and public health protection. These management approaches reflect a harmonized approach towards the assessment and management of risk for water-related infectious disease being applied by WHO. Numerical microbiological criteria for intestinal enterococci are proposed in the new Guidelines. These were developed using a novel approach to disease burden assessment, which has been applied to both recreational waters and urban air quality. This paper explains the scientific rationale and mathematical basis of the new approach, which is not presented in the WHO Guidelines for recreational waters.

Estimating the burden of disease from water, sanitation, and hygiene at a global level.

We estimated the disease burden from water, sanitation, and hygiene at the global level taking into account various disease outcomes, principally diarrheal diseases. The disability-adjusted life year (DALY) combines the burden from death and disability in a single index and permits the comparison of the burden from water, sanitation, and hygiene with the burden from other risk factors or diseases. We divided the world's population into typical exposure scenarios for 14 geographical regions. We then matched these scenarios with relative risk information obtained mainly from intervention studies. We estimated the disease burden from water, sanitation, and hygiene to be 4.0% of all deaths and 5.7% of the total disease burden (in DALYs) occurring worldwide, taking into account diarrheal diseases, schistosomiasis, trachoma, ascariasis, trichuriasis, and hookworm disease. Because we based these estimates mainly on intervention studies, this burden is largely preventable. Other water- and sanitation-related diseases remain to be evaluated. This preliminary estimation of the global disease burden caused by water, sanitation, and hygiene provides a basic model that could be further refined for national or regional assessments. This significant and avoidable burden suggests that it should be a priority for public health policy.