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Biomedical subjects

Timothy J Wade

Publications and source records attributed to Timothy J Wade.

13 recordsLinked to original sources

Water quality indicators and the risk of illness at beaches with nonpoint sources of fecal contamination.

BACKGROUND: Indicator bacteria are a good predictor of illness at marine beaches that have point sources of pollution with human fecal content. Few studies have addressed the utility of indicator bacteria where nonpoint sources are the dominant fecal input. Extrapolating current water-quality thresholds to such locations is uncertain. METHODS: In a cohort of 8797 beachgoers at Mission Bay, California, we measured baseline health at the time of exposure and 2 weeks later. Water samples were analyzed for bacterial indicators (enterococcus, fecal coliforms, total coliforms) using both traditional and nontraditional methods, ie, chromogenic substrate or quantitative polymerase chain reaction. A novel bacterial indicator (Bacteroides) and viruses (coliphage, adenovirus, norovirus) also were measured. Associations of 14 health outcomes with both water exposure and water quality indicators were assessed. RESULTS: Diarrhea and skin rash incidence were the only symptoms that were increased in swimmers compared with nonswimmers. The incidence of illness was not associated with any of the indicators that traditionally are used to monitor beaches. Among nontraditional water quality indicators, associations with illness were observed only for male-specific coliphage, although a low number of participants were exposed to water at times when coliphage was detected. CONCLUSIONS: Traditional fecal indicators currently used to monitor these beaches were not associated with health risks. These results suggest a need for alternative indicators of water quality where nonpoint sources are dominant fecal contributors.

Adolescent↗

Rapidly measured indicators of recreational water quality are predictive of swimming-associated gastrointestinal illness.

Standard methods to measure recreational water quality require at least 24 hr to obtain results, making it impossible to assess the quality of water within a single day. Methods to measure recreational water quality in <or=2 hr have been developed. Application of rapid methods could give considerably more accurate and timely assessments of recreational water quality. We conducted a prospective study of beachgoers at two Great Lakes beaches to examine the association between recreational water quality, obtained using rapid methods, and gastrointestinal (GI) illness after swimming. Beachgoers were asked about swimming and other beach activities and 10-12 days later were asked about the occurrence of GI symptoms. We tested water samples for Enterococcus and Bacteroides species using the quantitative polymerase chain reaction (PCR) method. We observed significant trends between increased GI illness and Enterococcus at the Lake Michigan beach and a positive trend for Enterococcus at the Lake Erie beach. The association remained significant for Enterococcus when the two beaches were combined. We observed a positive trend for Bacteroides at the Lake Erie beach, but no trend was observed at the Lake Michigan beach. Enterococcus samples collected at 0800 hr were predictive of GI illness that day. The association between Enterococcus and illness strengthened as time spent swimming in the water increased. This is the first study to show that water quality measured by rapid methods can predict swimming-associated health effects.

Adult↗

Inferences drawn from a risk assessment compared directly with a randomized trial of a home drinking water intervention.

Risk assessments and intervention trials have been used by the U.S. Environmental Protection Agency to estimate drinking water health risks. Seldom are both methods used concurrently. Between 2001 and 2003, illness data from a trial were collected simultaneously with exposure data, providing a unique opportunity to compare direct risk estimates of waterborne disease from the intervention trial with indirect estimates from a risk assessment. Comparing the group with water treatment (active) with that without water treatment (sham), the estimated annual attributable disease rate (cases per 10,000 persons per year) from the trial provided no evidence of a significantly elevated drinking water risk [attributable risk=-365 cases/year, sham minus active; 95% confidence interval (CI) , -2,555 to 1,825]. The predicted mean rate of disease per 10,000 persons per person-year from the risk assessment was 13.9 (2.5, 97.5 percentiles: 1.6, 37.7) assuming 4 log removal due to viral disinfection and 5.5 (2.5, 97.5 percentiles: 1.4, 19.2) assuming 6 log removal. Risk assessments are important under conditions of low risk when estimates are difficult to attain from trials. In particular, this assessment pointed toward the importance of attaining site-specific treatment data and the clear need for a better understanding of viral removal by disinfection. Trials provide direct risk estimates, and the upper confidence limit estimates, even if not statistically significant, are informative about possible upper estimates of likely risk. These differences suggest that conclusions about waterborne disease risk may be strengthened by the joint use of these two approaches. Key words: drinking water, gastrointestinal, intervention trial, microbial risk assessment, waterborne pathogens.

Algorithms↗

Chronic arsenic exposure and oxidative stress: OGG1 expression and arsenic exposure, nail selenium, and skin hyperkeratosis in Inner Mongolia.

Arsenic, a human carcinogen, is known to induce oxidative damage to DNA. In this study we investigated oxidative stress and As exposure by determining gene expression of OGG1, which codes for an enzyme, 8-oxoguanine DNA glycosylase, involved in removing 8-oxoguanine in As-exposed individuals. Bayingnormen (Ba Men) residents in Inner Mongolia are chronically exposed to As via drinking water. Water, toenail, and blood samples were collected from 299 Ba Men residents exposed to 0.34-826 microg/L As. RNA was isolated from blood, and mRNA levels of OGG1 were determined using real-time polymerase chain reaction. OGG1 expression levels were linked to As concentrations in drinking water and nails, selenium concentrations in nails, and skin hyperkeratosis. OGG1 expression was strongly associated with water As concentrations (p < 0.0001). Addition of the quadratic term significantly improved the fit compared with the linear model (p = 0.05) . The maximal OGG1 response was at the water As concentration of 149 microg/L. OGG1 expression was also significantly associated with toenail As concentrations (p = 0.015) but inversely associated with nail Se concentrations (p = 0.0095) . We found no significant differences in the As-induced OGG1 expression due to sex, smoking, or age even though the oldest group showed the strongest OGG1 response (p = 0.0001) . OGG1 expression showed a dose-dependent increased risk of skin hyperkeratosis in males (trend analysis, p = 0.02) , but the trend was not statistically significant in females. The results from this study provide a linkage between oxidative stress and As exposure in humans. OGG1 expression may be useful as a biomarker for assessing oxidative stress from As exposure.

Adolescent↗

Assessing waterborne risks: an introduction.

Information in this paper can help readers evaluate the results of epidemiologic studies of waterborne disease risks. It is important that readers understand the various epidemiologic study designs, their strengths and limitations, and potential biases. Terminology used by epidemiologists to describe disease risks can be confusing. Thus, readers should not only evaluate the adequacy of the information to estimate waterborne risks but should also understand how the risk was estimated. For example, one author's definition of attributable risk may be quite different from another author's in terms of the population to which the risk may apply and how it should be interpreted.

Communicable Diseases↗

A review of household drinking water intervention trials and an approach to the estimation of endemic waterborne gastroenteritis in the United States.

The incidence of acute gastrointestinal illness (AGI) attributable to public drinking water systems in the United States cannot be directly measured but must be estimated based on epidemiologic studies and other information. The randomized trial is one study design used to evaluate risks attributable to drinking water. In this paper, we review all published randomized trials of drinking water interventions in industrialized countries conducted among general immunocompetent populations. We then present an approach to estimating the incidence (number of cases) of AGI attributable annually to drinking water. To develop a national estimate, we integrate trial results with the estimated incidence of AGI using necessary assumptions about the estimated number of residents consuming different sources of drinking water and the relative quality of the water sources under different scenarios. Using this approach we estimate there to be 4.26-11.69 million cases of AGI annually attributable to public drinking water systems in the United States. We believe this preliminary estimate should be updated as new data become available.

Gastroenteritis↗

A randomized, controlled trial of in-home drinking water intervention to reduce gastrointestinal illness.

Trials have provided conflicting estimates of the risk of gastrointestinal illness attributable to tap water. To estimate this risk in an Iowa community with a well-run water utility with microbiologically challenged source water, the authors of this 2000-2002 study randomly assigned blinded volunteers to use externally identical devices (active device: 227 households with 646 persons; sham device: 229 households with 650 persons) for 6 months (cycle A). Each group then switched to the opposite device for 6 months (cycle B). The active device contained a 1-microm absolute ceramic filter and used ultraviolet light. Episodes of "highly credible gastrointestinal illness," a published measure of diarrhea, nausea, vomiting, and abdominal cramps, were recorded. Water usage was recorded with personal diaries and an electronic totalizer. The numbers of episodes in cycle A among the active and sham device groups were 707 and 672, respectively; in cycle B, the numbers of episodes were 516 and 476, respectively. In a log-linear generalized estimating equations model using intention-to-treat analysis, the relative rate of highly credible gastrointestinal illness (sham vs. active) for the entire trial was 0.98 (95% confidence interval: 0.86, 1.10). No reduction in gastrointestinal illness was detected after in-home use of a device designed to be highly effective in removing microorganisms from water.

Adolescent↗

Changes in beliefs identify unblinding in randomized controlled trials: a method to meet CONSORT guidelines.

Double-blinded trials are often considered the gold standard for research, but significant bias may result from unblinding of participants and investigators. Although the CONSORT guidelines discuss the importance of reporting "evidence that blinding was successful", it is unclear what constitutes appropriate evidence. Among studies reporting methods to evaluate blinding effectiveness, many have compared groups with respect to the proportions correctly identifying their intervention at the end of the trial. Instead, we reasoned that participants' beliefs, and not their correctness, are more directly associated with potential bias, especially in relation to self-reported health outcomes. During the Water Evaluation Trial performed in northern California in 1999, we investigated blinding effectiveness by sequential interrogation of participants about their "blinded" intervention assignment (active or placebo). Irrespective of group, participants showed a strong tendency to believe they had been assigned to the active intervention; this translated into a statistically significant intergroup difference in the correctness of participants' beliefs, even at the start of the trial before unblinding had a chance to occur. In addition, many participants (31%) changed their belief during the trial, suggesting that assessment of belief at a single time does not capture unblinding. Sequential measures based on either two or all eight questionnaires identified significant group-related differences in belief patterns that were not identified by the single, cross-sectional measure. In view of the relative insensitivity of cross-sectional measures, the minimal additional information in more than two assessments of beliefs and the risk of modifying participants' beliefs by repeated questioning, we conclude that the optimal means of assessing unblinding is an intergroup comparison of the change in beliefs (and not their correctness) between the start and end of a randomized controlled trial.

California↗

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

The subject paper describes a procedure for adjusting a risk model based upon a measure of personal exposure (the "UK personal exposure model") in order to attribute an expected rate of gastroenteritis among a group of swimmers to a mean recreational water quality value (enterococci per 100mL). We term the resulting model for group risk the "UK ecologic exposure model." The distinction is essential to establishing recreational water quality guidelines because exposures of individual bathers are not known from a water monitoring program, the only assessment available being some form of ecologic exposure such as a mean log indicator density. While the authors of the subject paper solved the UK ecologic exposure model for only a single point (that value of mean log10 enterococcus density which is expected to result in five extra cases of gastroenteritis per 100 swimmers), we extend their model to show the entire curve over a relevant range of densities. The resulting exposure-response curve is seen to not differ substantially from the existing USEPA model for "highly credible gastrointestinal illness" in marine waters. However, particularly since such correspondence is not guaranteed for future studies or for other existing epidemiological studies, we recommend the direct approach to evaluating ecologic exposure, such as used in the USEPA studies, rather than the indirect approach of the UK ecologic exposure model, given the number of untested assumptions that are necessary for accomplishing the latter.

Ecology↗

A pilot randomized, controlled trial of an in-home drinking water intervention among HIV + persons.

Although immunocompromised persons may be at increased risk for gastrointestinal illnesses, no trials investigating drinking water treatment and gastrointestinal illness in such patients have been published. Earlier results from San Francisco suggested an association (OR 6.76) between tap water and cryptosporidiosis among HIV + persons. The authors conducted a randomized, triple-blinded intervention trial of home water treatment in San Francisco, California, from April 2000 to May 2001. Fifty HIV-positive patients were randomized to externally identical active (N = 24) or sham (N = 26) treatment devices. The active device contained a filter and UV light; the sham provided no treatment. Forty-five (90%) of the participants completed the study and were successfully blinded. Illness was measured using 'highly credible gastrointestinal illness' (HCGI), a previously published measure. There were 31 episodes of HCGI during 1,797 person-days in the sham group and 16 episodes during 1,478 person-days in the active group. The adjusted relative risk was 3.34 (95% CI: 0.99-11.21) times greater in those with the sham device. The magnitude of the point estimate of the risk, its consistency with recently published observational data, and its relevance for drinking water choices by immunocompromised individuals support the need for larger trials.

Adult↗

Did a severe flood in the Midwest cause an increase in the incidence of gastrointestinal symptoms?

Severe flooding occurred in the midwestern United States in 2001. Since November 2000, coincidentally, data on gastrointestinal symptoms had been collected for a drinking water intervention study in a community along the Mississippi River that was affected by the flood. After the flood had subsided, the authors asked these subjects (n = 1,110) about their contact with floodwater. The objectives of this investigation were to determine whether rates of gastrointestinal illness were elevated during the flood and whether contact with floodwater was associated with increased risk of gastrointestinal illness. An increase in the incidence of gastrointestinal symptoms during the flood was observed (incidence rate ratio = 1.29, 95% confidence interval: 1.06, 1.58), and this effect was pronounced among persons with potential sensitivity to infectious gastrointestinal illness. Tap water consumption was not related to gastrointestinal symptoms before, during, or after the flood. An association between gastrointestinal symptoms and contact with floodwater was also observed, and this effect was pronounced in children. This appears to be the first report of an increase in endemic gastrointestinal symptoms in a longitudinal cohort prospectively observed during a flood. These findings suggest that severe climatic events can result in an increase in the endemic incidence of gastrointestinal symptoms in the United States.

Adult↗

Do U.S. Environmental Protection Agency water quality guidelines for recreational waters prevent gastrointestinal illness? A systematic review and meta-analysis.

Despite numerous studies, uncertainty remains about how water quality indicators can best be used in the regulation of recreational water. We conducted a systematic review of this topic with the goal of quantifying the association between microbial indicators of recreational water quality and gastrointestinal (GI) illness. A secondary goal was to evaluate the potential for GI illness below current guidelines. We screened 976 potentially relevant studies and from these identified 27 studies. From the latter, we determined summary relative risks for GI illness in relation to water quality indicator density. Our results support the use of enterococci in marine water at U.S. Environmental Protection Agency guideline levels. In fresh water, (Italic)Escherichia(/Italic) coli was a more consistent predictor of GI illness than are enterococci and other bacterial indicators. A log (base 10) unit increase in enterococci was associated with a 1.34 [95% confidence intervals (CI), 1.00-1.75] increase in relative risk in marine waters, and a log (base 10) unit increase in E. coli was associated with a 2.12 (95% CI, 0.925-4.85) increase in relative risk in fresh water. Indicators of viral contamination were strong predictors of GI illness in both fresh and marine environments. Significant heterogeneity was noted among the studies. In our analysis of heterogeneity, studies that used a nonswimming control group, studies that focused on children, and studies of athletic or other recreational events found elevated relative risks. Future studies should focus on the ability of new, more rapid and specific microbial methods to predict health effects, and estimating the risks of recreational water exposure among susceptible persons.

Diarrhea↗

Participant blinding and gastrointestinal illness in a randomized, controlled trial of an in-home drinking water intervention.

We conducted a randomized, triple-blinded home drinking water intervention trial to determine if a large study could be undertaken while successfully blinding participants. Households were randomized 50:50 to use externally identical active or sham treatment devices. We measured the effectiveness of blinding of participants by using a published blinding index in which values >0.5 indicate successful blinding. The principal health outcome measured was "highly credible gastrointestinal illness" (HCGI). Participants (n=236) from 77 households were successfully blinded to their treatment assignment. At the end of the study, the blinding index was 0.64 (95% confidence interval 0.51-0.78). There were 103 episodes of HCGI during 10,790 person-days at risk in the sham group and 82 episodes during 11,380 person-days at risk in the active treatment group. The incidence rate ratio of disease (adjusted for the clustered sampling) was 1.32 (95% CI 0.75, 2.33) and the attributable risk was 0.24 (95% CI -0.33, 0.57). These data confirm that participants can be successfully blinded to treatment group assignment during a randomized trial of an in-home drinking water intervention.

Adolescent↗