Effectiveness of filtering or decontaminating air to reduce or prevent respiratory infections: A systematic review.

Installation of technologies to remove or deactivate respiratory pathogens from indoor air is a plausible non-pharmaceutical infectious disease control strategy. OBJECTIVE: We undertook a systematic review of worldwide observational and experimental studies, published 1970-2022, to synthesise evidence about the effectiveness of suitable indoor air treatment technologies to prevent respiratory or gastrointestinal infections. METHODS: We searched for data about infection and symptom outcomes for persons who spent minimum 20 h/week in shared indoor spaces subjected to air treatment strategies hypothesised to change risk of respiratory or gastrointestinal infections or symptoms. RESULTS: Pooled data from 32 included studies suggested no net benefits of air treatment technologies for symptom severity or symptom presence, in absence of confirmed infection. Infection incidence was lower in three cohort studies for persons exposed to high efficiency particulate air filtration (RR 0.4, 95%CI 0.28-0.58, p < 0.001) and in one cohort study that combined ionisers with electrostatic nano filtration (RR 0.08, 95%CI 0.01-0.60, p = 0.01); other types of air treatment technologies and air treatment in other study designs were not strongly linked to fewer infections. The infection outcome data exhibited strong publication bias. CONCLUSIONS: Although environmental and surface samples are reduced after air treatment by several air treatment strategies, especially germicidal lights and high efficiency particulate air filtration, robust evidence has yet to emerge that these technologies are effective at reducing respiratory or gastrointestinal infections in real world settings. Data from several randomised trials have yet to report and will be welcome to the evidence base.

Development and temporal validation of clinical prediction models for 1-year disability and pain after lumbar decompressive surgery. The Norwich Lumbar Surgery Predictor (development version).

PURPOSE: To identify clinical predictors and build prediction models for 1-year patient-reported outcomes measures (PROMs) after lumbar decompressive surgery for disc herniation or spinal stenosis. METHODS: The study included 1835 cases, with or without additional single-level fusion, from a single centre from 2008 through 2020. General linear models imputed with 37 clinical variables identified 18 significant 1-year PROM predictors for retention in development models. Interaction of surgical indication with each predictor was tested. Temporal validation was conducted at the same centre on cases through 2021. R2 was used to measure goodness-of-fit, and area under curve (AUC) used to measure classification to a satisfactory symptom state (Oswestry Disability Index (ODI) ≤ 22; back or leg pain ≤ 30 out of 100). RESULTS: A total 1228 (67%) had complete data for inclusion in model development. Predictors of ODI were baseline PROMs (ODI, back pain, leg pain), work status, condition duration, previous lumbar operation, multiple-joint osteoarthritis, female, diabetes, current smoker, rheumatic disorder, lower limb arthroplasty, mobility aided, provider status, facet cyst, scoliosis, and age, with BMI significantly associated with stenosis. Temporal validation (n = 188) found the ODI model R2 was 0.29 (95% confidence intervals (CI) 0.18-0.40) and AUC was 0.74 (95% CI 0.67-0.81). Back and leg pain models had lower R2 (0.12-0.14) and AUC (0.68-0.69) values. CONCLUSION: Important PROM predictors are baseline PROMs, specific co-morbidities, work status, condition duration, previous lumbar operation, female, and smoking status. The ODI model predicted the likelihood of achieving a satisfactory state of both disability and pain.

Risk perception from the consumption of untreated drinking water in a small island community.

A small island community in Malaysia uses gravity-fed drinking water, and rejected water treatment by the authorities. This study was conducted to evaluate the community's risk perception towards their untreated water supply by interviewing one adult per household in four out of eight villages on the island. The survey asked questions on risk perception, socioeconomic characteristics, and perception of water supply quality. Water samples were collected from a total of 24 sampling locations across the four villages, and 91.7% of them were positive for E.coli. The study surveyed 218 households and found that 61.5% of respondents agreed to some degree that the water is safe to drink without treatment, while 67.9% of respondents disagreed to some degree that drinking tap water is associated with health risks, and 73.3% of respondents agreed to some degree that it is safe to drink directly from taps that are fitted with water filters. Using factor analysis to group the risk perception questions and multivariable GLM to explore relationships with underlying factors, the study found that older respondents, lower income level, positive water odour perception and positive water supply reliability perception lowers risk perception. The village of residence also significantly affects the risk perception level in the model.

Spatial Risk Factors for Pillar 1 COVID-19 Excess Cases and Mortality in Rural Eastern England, UK.

Understanding is still developing about spatial risk factors for COVID-19 infection or mortality. This is a secondary analysis of patient records in a confined area of eastern England, covering persons who tested positive for SARS-CoV-2 through end May 2020, including dates of death and residence area. We obtained residence area data on air quality, deprivation levels, care home bed capacity, age distribution, rurality, access to employment centers, and population density. We considered these covariates as risk factors for excess cases and excess deaths in the 28 days after confirmation of positive Covid status relative to the overall case load and death recorded for the study area as a whole. We used the conditional autoregressive Besag-York-Mollie model to investigate the spatial dependency of cases and deaths allowing for a Poisson error structure. Structural equation models were applied to clarify relationships between predictors and outcomes. Excess case counts or excess deaths were both predicted by the percentage of population age 65 years, care home bed capacity and less rurality: older population and more urban areas saw excess cases. Greater deprivation did not correlate with excess case counts but was significantly linked to higher mortality rates after infection. Neither excess cases nor excess deaths were predicted by population density, travel time to local employment centers, or air quality indicators. Only 66% of mortality was explained by locally high case counts. Higher deprivation clearly linked to higher COVID-19 mortality separate from wider community prevalence and other spatial risk factors.

Efficacy of halofuginone products to prevent or treat cryptosporidiosis in bovine calves: a systematic review and meta-analyses.

A prior systematic review on the efficacy of halofuginone (HFG) treatment to prevent or treat cryptosporidiosis in bovine calves was inconclusive. We undertook an updated synthesis and meta-analyses on key outcomes for the treatment of calves with HFG. Evaluated outcomes were oocyst shedding, diarrhoea, mortality and weight gain. Experiments had to describe results for same age animals in contemporary arms. Most doses were 100-150 mcg kg-1 day-1. Results were subgrouped by study design, experiments with the lowest risk of bias and lack of industry funding. Eighteen articles were found that described 25 experiments. Most evidence came from randomized controlled trials in Europe. Significantly lower incidence of oocyst shedding, diarrhoea burden and mortality was reported when treatment started before calves were 5 days old. Most studies reported on outcomes for animals up to at least 28 days old. Publication bias was possible in all outcomes and seemed especially likely for diarrhoea outcomes. Beneficial results when HFG treatment was initiated in calves older than 5 days were also found. Prophylactic treatment to prevent cryptosporidiosis is effective in preventing multiple negative outcomes and is beneficial to calf health and will result in a reduction of environmental contamination by Cryptosporidium oocysts.

Introduction to and spread of COVID-19-like illness in care homes in Norfolk, UK.

BACKGROUND: Residential care homes for the elderly are important settings for transmission of the SARS-CoV-2 virus that causes COVID-19 disease. METHODS: We undertook secondary analysis of 248 care homes in Norfolk, UK. The dataset counted nurses, care workers and non-care workers, their status (available, absent due to leave or sickness and extra staff needed to address the coronavirus pandemic) and residents (if any) with suspected COVID-19 in the period 6 April to 6 May 2020. Concurrent descriptions of access by the home to personal protection equipment (PPE: gloves, masks, eye protection, aprons and sanitizer) were in the data. PPE access was categorized as (most to least) green, amber or red. We undertook two-stage modelling, first for suspected COVID-19 cases amongst residents and second relating any increases in case counts after introduction to staffing or PPE levels. RESULTS: Counts of non-care workers had strongest relationships (P < 0.05) to introduction of suspected SARS-CoV-2 to the homes. Higher staff levels and more severe PPE shortages were linked to higher case counts (P < 0.05) during the monitoring period. CONCLUSION: Managing aspects of staff interaction with residents and some working practices might reduce ingression to and spread of COVID-19-like illness within care homes.

Limiting global-mean temperature increase to 1.5-2 °C could reduce the incidence and spatial spread of dengue fever in Latin America.

The Paris Climate Agreement aims to hold global-mean temperature well below 2 °C and to pursue efforts to limit it to 1.5 °C above preindustrial levels. While it is recognized that there are benefits for human health in limiting global warming to 1.5 °C, the magnitude with which those societal benefits will be accrued remains unquantified. Crucial to public health preparedness and response is the understanding and quantification of such impacts at different levels of warming. Using dengue in Latin America as a study case, a climate-driven dengue generalized additive mixed model was developed to predict global warming impacts using five different global circulation models, all scaled to represent multiple global-mean temperature assumptions. We show that policies to limit global warming to 2 °C could reduce dengue cases by about 2.8 (0.8-7.4) million cases per year by the end of the century compared with a no-policy scenario that warms by 3.7 °C. Limiting warming further to 1.5 °C produces an additional drop in cases of about 0.5 (0.2-1.1) million per year. Furthermore, we found that by limiting global warming we can limit the expansion of the disease toward areas where incidence is currently low. We anticipate our study to be a starting point for more comprehensive studies incorporating socioeconomic scenarios and how they may further impact dengue incidence. Our results demonstrate that although future climate change may amplify dengue transmission in the region, impacts may be avoided by constraining the level of warming.

The COVID University Challenge: A Hazard Analysis of Critical Control Points Assessment of the Return of Students to Higher Education Establishments.

The COVID-19 pandemic has disrupted economies and societies throughout the world since early 2020. Education is especially affected, with schools and universities widely closed for long periods. People under 25 years have the lowest risk of severe disease but their activities can be key to persistent ongoing community transmission. A challenge arose for how to provide education, including university level, without the activities of students increasing wider community SARS-CoV-2 infections. We used a Hazard Analysis of Critical Control Points (HACCP) framework to assess the risks associated with university student activity and recommend how to mitigate these risks. This tool appealed because it relies on multiagency collaboration and interdisciplinary expertise and yet is low cost, allowing rapid generation of evidence-based recommendations. We identified key critical control points associated with university student' activities, lifestyle, and interaction patterns both on-and-off campus. Unacceptable contact thresholds and the most up-to-date guidance were used to identify levels of risk for potential SARS-CoV-2 transmission, as well as recommendations based on existing research and emerging evidence for strategies that can reduce the risks of transmission. Employing the preventative measures we suggest can reduce the risks of SARS-CoV-2 transmission among and from university students. Reduction of infectious disease transmission in this demographic will reduce overall community transmission, lower demands on health services and reduce risk of harm to clinically vulnerable individuals while allowing vital education activity to continue. HACCP assessment proved a flexible tool for risk analysis in a specific setting in response to an emerging infectious disease threat. Systematic approaches to assessing hazards and risk critical control points (#HACCP) enable robust strategies for protecting students and staff in HE settings during #COVID19 pandemic.

Impact of non-pharmaceutical interventions against COVID-19 in Europe in 2020: a quasi-experimental non-equivalent group and time series design study.

IntroductionThe current pandemic of coronavirus disease (COVID-19) is unparalleled in recent history as are the social distancing interventions that have led to a considerable halt on the economic and social life of so many countries.AimWe aimed to generate empirical evidence about which social distancing measures had the most impact in reducing case counts and mortality.MethodsWe report a quasi-experimental (observational) study of the impact of various interventions for control of the outbreak through 24 April 2020. Chronological data on case numbers and deaths were taken from the daily published figures by the European Centre for Disease Prevention and Control and dates of initiation of various control strategies from the Institute of Health Metrics and Evaluation website and published sources. Our complementary analyses were modelled in R using Bayesian generalised additive mixed models and in STATA using multilevel mixed-effects regression models.ResultsFrom both sets of modelling, we found that closure of education facilities, prohibiting mass gatherings and closure of some non-essential businesses were associated with reduced incidence whereas stay-at-home orders and closure of additional non-essential businesses was not associated with any independent additional impact.ConclusionsOur findings are that schools and some non-essential businesses operating 'as normal' as well as allowing mass gatherings were incompatible with suppressing disease spread. Closure of all businesses and stay at home orders are less likely to be required to keep disease incidence low. Our results help identify what were the most effective non-pharmaceutical interventions in this period.

Detection of Shiga toxin-encoding genes in small community water supplies.

Shiga toxin (Stx), one of the most potent bacterial toxins known, can cause bloody diarrhea, hemolytic uremic syndrome, kidney failure and death. The aim of this pilot was to investigate the occurrence of Shiga toxin-encoding genes, stx (stx1 and stx2) from total coliform (TC) and E. coli positive samples from small community water systems. After aliquots for TC and E. coli analyses were removed, the remnant volume of the samples was enriched, following a protocol developed for this study. Fifty-two per cent of the samples tested by multiplex PCR were positive for the presence of the stx genes; this percentage was higher in raw water samples. The stx2 gene was more abundant. Testing larger volumes of the samples increase the sensitivity of our assay, providing an alternative protocol for the detection of Shiga toxin-producing E. coli (STEC) that might be missed by the TC assay. This study confirms the presence of Stx encoding genes in source and distributed water for all systems sampled and suggests STEC as a potential health risk in small systems.

Can economic indicators predict infectious disease spread? A cross-country panel analysis of 13 European countries.

Aims: It is unclear how economic factors impact on the epidemiology of infectious disease. We evaluated the relationship between incidence of selected infectious diseases and economic factors, including economic downturn, in 13 European countries between 1970 and 2010. Methods: Data were obtained from national communicable disease surveillance centres. Negative binomial forms of the generalised additive model (GAM) and the generalised linear model were tested to see which best reflected transmission dynamics of: diphtheria, pertussis, measles, meningococcal disease, hepatitis B, gonorrhoea, syphilis, hepatitis A and salmonella. Economic indicators were gross domestic product per capita (GDPpc), unemployment rates and (economic) downturn. Results: GAM models produced the best goodness-of-fit results. The relationship between GDPpc and disease incidence was often non-linear. Strength and directions of association between population age, tertiary education levels, GDPpc and unemployment were disease dependent. Overdispersion for almost all diseases validated the assumption of a negative binomial relationship. Downturns were not independently linked to disease incidence. Conclusions: Social and economic factors can be correlated with many infections. However, the trend is not always in the same direction, and these associations are often non-linear. Economic downturn or recessions as indicators of increased disease risk may be better replaced by GDPpc or unemployment measures.

Systematic review of modifiable risk factors shows little evidential support for most current practices in Cryptosporidium management in bovine calves.

Cryptosporidiosis is common in young calves, causing diarrhoea, delayed growth, poor condition and excess mortality. No vaccine or cure exists, although symptomatic onset may be delayed with some chemoprophylactics. Other response and management strategies have focused on nutritional status, cleanliness and biosecurity. We undertook a systematic review of observational studies to identify risk or protective factors that could prevent Cryptosporidium parvum infection in calves. Included studies used multivariate analysis within cohort, cross-sectional or case-control designs, of risk factors among young calves, assessing C. parvum specifically. We tabulated data on characteristics and study quality and present narrative synthesis. Fourteen eligible studies were found; three of which were higher quality. The most consistent evidence suggested that risk of C. parvum infection increased when calves had more contact with other calves, were in larger herds or in organic production. Hard flooring reduced risk of infection and calves tended to have more cryptosporidiosis during warm and wet weather. While many other factors were not found to be associated with C. parvum infection, analyses were usually badly underpowered, due to clustering of management factors. Trials are needed to assess effects of manipulating calf contact, herd size, organic methods, hard flooring and temperature. Other factors need to be assessed in larger observational studies with improved disaggregation of potential risk factors.

Community use of face masks and similar barriers to prevent respiratory illness such as COVID-19: a rapid scoping review.

BackgroundEvidence for face-mask wearing in the community to protect against respiratory disease is unclear.AimTo assess effectiveness of wearing face masks in the community to prevent respiratory disease, and recommend improvements to this evidence base.MethodsWe systematically searched Scopus, Embase and MEDLINE for studies evaluating respiratory disease incidence after face-mask wearing (or not). Narrative synthesis and random-effects meta-analysis of attack rates for primary and secondary prevention were performed, subgrouped by design, setting, face barrier type, and who wore the mask. Preferred outcome was influenza-like illness. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) quality assessment was undertaken and evidence base deficits described.Results33 studies (12 randomised control trials (RCTs)) were included. Mask wearing reduced primary infection by 6% (odds ratio (OR): 0.94; 95% CI: 0.75-1.19 for RCTs) to 61% (OR: 0.85; 95% CI: 0.32-2.27; OR: 0.39; 95% CI: 0.18-0.84 and OR: 0.61; 95% CI: 0.45-0.85 for cohort, case-control and cross-sectional studies respectively). RCTs suggested lowest secondary attack rates when both well and ill household members wore masks (OR: 0.81; 95% CI: 0.48-1.37). While RCTs might underestimate effects due to poor compliance and controls wearing masks, observational studies likely overestimate effects, as mask wearing might be associated with other risk-averse behaviours. GRADE was low or very low quality.ConclusionWearing face masks may reduce primary respiratory infection risk, probably by 6-15%. It is important to balance evidence from RCTs and observational studies when their conclusions widely differ and both are at risk of significant bias. COVID-19-specific studies are required.

Misinformation making a disease outbreak worse: outcomes compared for influenza, monkeypox, and norovirus.

Health misinformation can exacerbate infectious disease outbreaks. Especially pernicious advice could be classified as "fake news": manufactured with no respect for accuracy and often integrated with emotive or conspiracy-framed narratives. We built an agent-based model that simulated separate but linked circulating contagious disease and sharing of health advice (classified as useful or harmful). Such advice has potential to influence human risk-taking behavior and therefore the risk of acquiring infection, especially as people are more likely in observed social networks to share bad advice. We test strategies proposed in the recent literature for countering misinformation. Reducing harmful advice from 50% to 40% of circulating information, or making at least 20% of the population unable to share or believe harmful advice, mitigated the influence of bad advice in the disease outbreak outcomes. How feasible it is to try to make people "immune" to misinformation or control spread of harmful advice should be explored.

The implications of three major new trials for the effect of water, sanitation and hygiene on childhood diarrhea and stunting: a consensus statement.

BACKGROUND: Three large new trials of unprecedented scale and cost, which included novel factorial designs, have found no effect of basic water, sanitation and hygiene (WASH) interventions on childhood stunting, and only mixed effects on childhood diarrhea. Arriving at the inception of the United Nations' Sustainable Development Goals, and the bold new target of safely managed water, sanitation and hygiene for all by 2030, these results warrant the attention of researchers, policy-makers and practitioners. MAIN BODY: Here we report the conclusions of an expert meeting convened by the World Health Organization and the Bill and Melinda Gates Foundation to discuss these findings, and present five key consensus messages as a basis for wider discussion and debate in the WASH and nutrition sectors. We judge these trials to have high internal validity, constituting good evidence that these specific interventions had no effect on childhood linear growth, and mixed effects on childhood diarrhea. These results suggest that, in settings such as these, more comprehensive or ambitious WASH interventions may be needed to achieve a major impact on child health. CONCLUSION: These results are important because such basic interventions are often deployed in low-income rural settings with the expectation of improving child health, although this is rarely the sole justification. Our view is that these three new trials do not show that WASH in general cannot influence child linear growth, but they do demonstrate that these specific interventions had no influence in settings where stunting remains an important public health challenge. We support a call for transformative WASH, in so much as it encapsulates the guiding principle that - in any context - a comprehensive package of WASH interventions is needed that is tailored to address the local exposure landscape and enteric disease burden.

Climate, human behaviour or environment: individual-based modelling of Campylobacter seasonality and strategies to reduce disease burden.

BACKGROUND: With over 800 million cases globally, campylobacteriosis is a major cause of food borne disease. In temperate climates incidence is highly seasonal but the underlying mechanisms are poorly understood, making human disease control difficult. We hypothesised that observed disease patterns reflect complex interactions between weather, patterns of human risk behaviour, immune status and level of food contamination. Only by understanding these can we find effective interventions. METHODS: We analysed trends in human Campylobacter cases in NE England from 2004 to 2009, investigating the associations between different risk factors and disease using time-series models. We then developed an individual-based (IB) model of risk behaviour, human immunological responses to infection and environmental contamination driven by weather and land use. We parameterised the IB model for NE England and compared outputs to observed numbers of reported cases each month in the population in 2004-2009. Finally, we used it to investigate different community level disease reduction strategies. RESULTS: Risk behaviours like countryside visits (t = 3.665, P < 0.001 and t = - 2.187, P = 0.029 for temperature and rainfall respectively), and consumption of barbecued food were strongly associated with weather, (t = 3.219, P = 0.002 and t = 2.015, P = 0.045 for weekly average temperature and average maximum temperature respectively) and also rain (t = 2.254, P = 0.02527). This suggests that the effect of weather was indirect, acting through changes in risk behaviour. The seasonal pattern of cases predicted by the IB model was significantly related to observed patterns (r = 0.72, P < 0.001) indicating that simulating risk behaviour could produce the observed seasonal patterns of cases. A vaccination strategy providing short-term immunity was more effective than educational interventions to modify human risk behaviour. Extending immunity to 1 year from 20 days reduced disease burden by an order of magnitude (from 2412-2414 to 203-309 cases per 50,000 person-years). CONCLUSIONS: This is the first interdisciplinary study to integrate environment, risk behaviour, socio-demographics and immunology to model Campylobacter infection, including pathways to mitigation. We conclude that vaccination is likely to be the best route for intervening against campylobacteriosis despite the technical problems associated with understanding both the underlying human immunology and genetic variation in the pathogen, and the likely cost of vaccine development.

Calcium imaging and dynamic causal modelling reveal brain-wide changes in effective connectivity and synaptic dynamics during epileptic seizures.

Pathophysiological explanations of epilepsy typically focus on either the micro/mesoscale (e.g. excitation-inhibition imbalance), or on the macroscale (e.g. network architecture). Linking abnormalities across spatial scales remains difficult, partly because of technical limitations in measuring neuronal signatures concurrently at the scales involved. Here we use light sheet imaging of the larval zebrafish brain during acute epileptic seizure induced with pentylenetetrazole. Spectral changes of spontaneous neuronal activity during the seizure are then modelled using neural mass models, allowing Bayesian inference on changes in effective network connectivity and their underlying synaptic dynamics. This dynamic causal modelling of seizures in the zebrafish brain reveals concurrent changes in synaptic coupling at macro- and mesoscale. Fluctuations of both synaptic connection strength and their temporal dynamics are required to explain observed seizure patterns. These findings highlight distinct changes in local (intrinsic) and long-range (extrinsic) synaptic transmission dynamics as a possible seizure pathomechanism and illustrate how our Bayesian model inversion approach can be used to link existing neural mass models of seizure activity and novel experimental methods.

(Re-) conceptualising vulnerability as a part of risk in global health emergency response: updating the pressure and release model for global health emergencies.

Vulnerability has become a key concept in emergency response research and is being critically discussed across several disciplines. While the concept has been adopted into global health, its conceptualisation and especially its role in the conceptualisation of risk and therefore in risk assessments is still lacking. This paper uses the risk concept pioneered in hazard research that assumes that risk is a function of the interaction between hazard and vulnerability rather than the neo-liberal conceptualisation of vulnerability and vulnerable groups and communities. By seeking to modify the original pressure and release model, the paper unpacks the representation or lack of representation of vulnerability in risk assessments in global health emergency response and discusses what benefits can be gained from making the underlying assumptions about vulnerability, which are present whether vulnerability is sufficiently conceptualised and consciously included or not, explicit. The paper argues that discussions about risk in global health emergencies should be better grounded in a theoretical understanding of the concept of vulnerability and that this theoretical understanding needs to inform risk assessments which implicitly used the concept of vulnerability. By using the hazard research approach to vulnerability, it offers an alternative narrative with new perspectives on the value and limits of vulnerability as a concept and a tool.

Emerging pathogens and deliberate attacks on European water supplies: a scenario planning workshop.

Microbiological contamination of drinking water supplies is an ever-present concern for water utility managers. Most such threats are routine, well-recognised and described. Therefore, they can usually be prevented using standard protection measures. Incidents involving emerging pathogens and malicious attacks are inherently less predictable. In a multi-stage process over one day, participants with backgrounds in microbiology, medicine, infrastructure, data analysis, environmental or public health and facility management developed qualitative scenarios on potential threats posed by either an emergent pathogen in or a microbiological attack on drinking water supplies in a European country. Participants were guided via structured activities to identify key factors that would impact the magnitude and severity of such an emergency. Plausible variant states for each key factor were determined, and participants constructed sequences of events to create scenario outlines. Five scenarios in outline form are reported which incorporate genuine possible future events as well as pathogens of international concern. Common features that would exacerbate all scenarios were under-investment in public services, inadequate water quality testing, and monitoring and lack of resources to keep water supplies safe. Participant evaluation of their scenario planning experience was broadly very positive and the scenario planning process was received as credible and relevant.

Impact of drinking water, sanitation and handwashing with soap on childhood diarrhoeal disease: updated meta-analysis and meta-regression.

OBJECTIVES: Safe drinking water, sanitation and hygiene are protective against diarrhoeal disease; a leading cause of child mortality. The main objective was an updated assessment of the impact of unsafe water, sanitation and hygiene (WaSH) on childhood diarrhoeal disease. METHODS: We undertook a systematic review of articles published between 1970 and February 2016. Study results were combined and analysed using meta-analysis and meta-regression. RESULTS: A total of 135 studies met the inclusion criteria. Several water, sanitation and hygiene interventions were associated with lower risk of diarrhoeal morbidity. Point-of-use filter interventions with safe storage reduced diarrhoea risk by 61% (RR = 0.39; 95% CI: 0.32, 0.48); piped water to premises of higher quality and continuous availability by 75% and 36% (RR = 0.25 (0.09, 0.67) and 0.64 (0.42, 0.98)), respectively compared to a baseline of unimproved drinking water; sanitation interventions by 25% (RR = 0.75 (0.63, 0.88)) with evidence for greater reductions when high sanitation coverage is reached; and interventions promoting handwashing with soap by 30% (RR = 0.70 (0.64, 0.77)) vs. no intervention. Results of the analysis of sanitation and hygiene interventions are sensitive to certain differences in study methods and conditions. Correcting for non-blinding would reduce the associations with diarrhoea to some extent. CONCLUSIONS: Although evidence is limited, results suggest that household connections of water supply and higher levels of community coverage for sanitation appear particularly impactful which is in line with targets of the Sustainable Development Goals.