Estimating the burden of acute gastrointestinal illness due to Giardia, Cryptosporidium, Campylobacter, E. coli O157 and norovirus associated with private wells and small water systems in Canada.

Waterborne illness related to the consumption of contaminated or inadequately treated water is a global public health concern. Although the magnitude of drinking water-related illnesses in developed countries is lower than that observed in developing regions of the world, drinking water is still responsible for a proportion of all cases of acute gastrointestinal illness (AGI) in Canada. The estimated burden of endemic AGI in Canada is 20·5 million cases annually - this estimate accounts for under-reporting and under-diagnosis. About 4 million of these cases are domestically acquired and foodborne, yet the proportion of waterborne cases is unknown. There is evidence that individuals served by private systems and small community systems may be more at risk of waterborne illness than those served by municipal drinking water systems in Canada. However, little is known regarding the contribution of these systems to the overall drinking water-related AGI burden in Canada. Private water supplies serve an estimated 12% of the Canadian population, or ~4·1 million people. An estimated 1·4 million (4·1%) people in Canada are served by small groundwater (2·6%) and surface water (1·5%) supplies. The objective of this research is to estimate the number of AGI cases attributable to water consumption from these supplies in Canada using a quantitative microbial risk assessment (QMRA) approach. This provides a framework for others to develop burden of waterborne illness estimates for small water supplies. A multi-pathogen QMRA of Giardia, Cryptosporidium, Campylobacter, E. coli O157 and norovirus, chosen as index waterborne pathogens, for various source water and treatment combinations was performed. It is estimated that 103 230 AGI cases per year are due to the presence of these five pathogens in drinking water from private and small community water systems in Canada. In addition to providing a mechanism to assess the potential burden of AGI attributed to small systems and private well water in Canada, this research supports the use of QMRA as an effective source attribution tool when there is a lack of randomized controlled trial data to evaluate the public health risk of an exposure source. QMRA is also a powerful tool for identifying existing knowledge gaps on the national scale to inform future surveillance and research efforts.

Estimating the number of cases of acute gastrointestinal illness (AGI) associated with Canadian municipal drinking water systems.

The estimated burden of endemic acute gastrointestinal illness (AGI) annually in Canada is 20·5 million cases. Approximately 4 million of these cases are domestically acquired and foodborne, yet the proportion of waterborne cases is unknown. A number of randomized controlled trials have been completed to estimate the influence of tap water from municipal drinking water plants on the burden of AGI. In Canada, 83% of the population (28 521 761 people) consumes tap water from municipal drinking water plants serving >1000 people. The drinking water-related AGI burden associated with the consumption of water from these systems in Canada is unknown. The objective of this research was to estimate the number of AGI cases attributable to consumption of drinking water from large municipal water supplies in Canada, using data from four household drinking water intervention trials. Canadian municipal water treatment systems were ranked into four categories based on source water type and quality, population size served, and treatment capability and barriers. The water treatment plants studied in the four household drinking water intervention trials were also ranked according to the aforementioned criteria, and the Canadian treatment plants were then scored against these criteria to develop four AGI risk groups. The proportion of illnesses attributed to distribution system events vs. source water quality/treatment failures was also estimated, to inform the focus of future intervention efforts. It is estimated that 334 966 cases (90% probability interval 183 006-501 026) of AGI per year are associated with the consumption of tap water from municipal systems that serve >1000 people in Canada. This study provides a framework for estimating the burden of waterborne illness at a national level and identifying existing knowledge gaps for future research and surveillance efforts, in Canada and abroad.

Comparing the microbial risks associated with household drinking water supplies used in peri-urban communities of Phnom Penh, Cambodia.

Most Cambodians lack access to a safe source of drinking water. Piped distribution systems are typically limited to major urban centers in Cambodia, and the remaining population relies on a variety of surface, rain, and groundwater sources. This study examines the household water supplies available to Phnom Penh's resettled peri-urban residents through a case-study approach of two communities. A quantitative microbial risk assessment is performed to assess the level of diarrheal disease risk faced by community members due to microbial contamination of drinking water. Risk levels found in this study exceed those associated with households consuming piped water. Filtered and boiled rain and tank water stored in a kettle, bucket/cooler, bucket with spigot or a 500 mL bottle were found to provide risk levels within one order-of-magnitude to the piped water available in Phnom Penh. Two primary concerns identified are the negation of the risk reductions gained by boiling due to prevailing poor storage practices and the use of highly contaminated source water.

A systematic review of waterborne disease burden methodologies from developed countries.

The true incidence of endemic acute gastrointestinal illness (AGI) attributable to drinking water in Canada is unknown. Using a systematic review framework, the literature was evaluated to identify methods used to attribute AGI to drinking water. Several strategies have been suggested or applied to quantify AGI attributable to drinking water at a national level. These vary from simple point estimates, to quantitative microbial risk assessment, to Monte Carlo simulations, which rely on assumptions and epidemiological data from the literature. Using two methods proposed by researchers in the USA, this paper compares the current approaches and key assumptions. Knowledge gaps are identified to inform future waterborne disease attribution estimates. To improve future estimates, there is a need for robust epidemiological studies that quantify the health risks associated with small, private water systems, groundwater systems and the influence of distribution system intrusions on risk. Quantification of the occurrence of enteric pathogens in water supplies, particularly for groundwater, is needed. In addition, there are unanswered questions regarding the susceptibility of vulnerable sub-populations to these pathogens and the influence of extreme weather events (precipitation) on AGI-related health risks. National centralized data to quantify the proportions of the population served by different water sources, by treatment level, source water quality, and the condition of the distribution system infrastructure, are needed.

Two risk assessments: Evaluating the use of indicator HF183 Bacteroides versus pathogen measurements for modelling recreational illness risks in an urban watershed.

The purpose of this study was to evaluate the performance of HF183 Bacteroides for estimating pathogen exposures during recreational water activities. We compared the use of Bacteroides-based exposure assessment to exposure assessment that relied on pathogen measurements. We considered two types of recreational water sites: those impacted by combined sewer overflows (CSOs) and those not impacted by CSOs. Samples from CSO-impacted and non-CSO-impacted urban creeks were analysed by quantitative polymerase chain reaction (qPCR) for HF183 Bacteroides and eight human gastrointestinal pathogens. Exposure assessment was conducted two ways for each type of site (CSO-impacted vs. non-CSO impacted): 1) by estimating pathogen concentrations from HF183 Bacteroides concentrations using published ratios of HF183 to pathogens in sewage and 2) by estimating pathogen concentrations from qPCR measurements. QMRA (quantitative microbial risk assessment) was then conducted for swimming, wading, and fishing exposures. Overall, mean risk estimates varied from 0.27 to 53 illnesses per 1,000 recreators depending on exposure assessment, site, activity, and norovirus dose-response model. HF183-based exposure assessment identified CSO-impacted sites as higher risk, and the recommended HF183 risk-based threshold of 525 genomic copies per 100 mL was generally protective of public health at the CSO-impacted sites but was not as protective at the non-CSO-impacted sites. In the context of our urban watershed, HF183-based exposure assessment over- and under-estimated risk relative to exposure assessment based on pathogen measurements, and the etiology of predicted pathogen-specific illnesses differed significantly. Across all sites, the HF183 model overestimated risk for norovirus, adenovirus, and Campylobacter jejuni, and it underestimated risk for E. coli and Cryptosporidium. To our knowledge, this study is the first to directly compare health risk estimates using HF183 and empirical pathogen measurements from the same waterways. Our work highlights the importance of site-specific hazard identification and exposure assessment to decide whether HF183 is applicable for monitoring risk.

Sequential UV- and chlorine-based disinfection to mitigate Escherichia coli in drinking water biofilms.

This study was designed to examine the potential downstream benefits of sequential disinfection to control the persistence of Escherichia coli under conditions relevant to drinking water distribution systems. Eight annular reactors (four polycarbonate and four cast iron) were setup in parallel to address various factors that could influence biofilm growth in distribution systems. Eight reactors were treated with chlorine, chlorine dioxide and monochloramine alone or in combination with UV to examine the effects on Escherichia coli growth and persistence in both the effluent and biofilm. In general, UV-treated systems in combination with chlorine or chlorine dioxide and monochloramine achieved greater log reductions in both effluent and biofilm than systems treated with chlorine-based disinfectants alone. However, during UV-low chlorine disinfection, E. coli was found to persist at low levels, suggesting that the UV treatment had instigated an adaptive mutation. During UV-chlorine-dioxide treatment, the E. coli that was initially below the detection limit reappeared during a low level of disinfection (0.2 mg/L) in the cast iron systems. Chloramine was shown to be effective in disinfecting suspended E. coli in the effluent but was unable to reduce biofilm counts to below the detection limit. Issues such as repair mechanism of E. coli and nitrification could help explain some of these aberrations. Improved understanding of the ability of chlorine-based disinfectant in combination with UV to provide sufficient disinfection will ultimately effect in improved management and safety of drinking water.

Effects of vasopressin deficiency, age, and stress on stomach ulcer induction in rats.

Susceptibility to ulceration induced by restraint, restraint plus intermittent shock, and activity stress was studied in 6 week and 18 week old Brattleboro and Long-Evans rats. Older animals developed more glandular ulcers than younger animals with Brattleboro rats having significantly greater ulceration than Long-Evans rats in both conditions. With activity stress, younger subjects developed significantly more glandular ulcers than older subjects; whereas, older subjects developed significantly more nonglandular ulcers than younger subjects. In both instances, the ulceration was significantly greater in Brattleboro rats than in Long-Evans rats. There were significantly high correlations among running behavior, survival time, and the development of glandular ulcers in younger animals exposed to activity stress. The presence of vasopressin, as well as the age of the subject and the nature of the stress, influences the type and degree of stomach pathology induced.

Effects of vasopressin replacement during food-restriction stress.

The effects of subcutaneous injections of vasopressin in vasopressin-deficient (Brattleboro or DI) rats were observed during nonstress (habituation) and stress (food-restriction) conditions as compared to other rats. Four groups of animals were employed: 1) Long-Evans (LE) rats that were food restricted with no injections (normal control animals), 2) DI rats that were food restricted with no injections, 3) DI rats injected with vasopressin, and 4) DI rats injected with peanut oil (vehicle). The parameters studied were: body weight, food intake, water intake, and gastric ulcer formation. With respect to body weight, water intake, and ulcer formation, two sets of animals emerged. The vasopressin-injected DI rats resembled the LE control rats, whereas the peanut oil-injected DI rats were similar to the DI rats with no injections. The former set of animals showed a higher body weight, reduced water intake, and fewer gastric ulcers than the latter set of animals. Thus the vasopressin-injected DI rats and the LE control rats could cope with the stress of food restriction, but the peanut oil-injected DI rats and the DI rats with no injections could not.

Vasopressin deficiency and the modulation of consummatory behavior.

This study examined patterns of consummatory behavior in normal and vasopressin-deficient rats under ad lib and food-restricted conditions. Differing patterns of intake of food, water, sucrose, and saccharin were found in the two groups. During the ad lib period, the normal rats gained more weight and ate significantly more food than vasopressin-deficient rats. The vasopressin-deficient animals consumed significantly more sucrose than normal animals during this period. No significant differences in body weight, food intake, sucrose intake, or saccharin intake were noted during the food-restricted period between the two groups. During the food-restricted condition the normal animals showed a cyclic pattern of food, sucrose, and saccharin intake. This cyclic pattern of intake was absent in vasopressin-deficient animals. A vasopressin-serotonin interaction is hypothesized as a possible mechanism producing the differences in the two strains of animals. In addition, the data support the position that food consumption is regulated primarily by caloric and/or nutritional factors.

Vasopressin, corticosterone levels, and gastric ulcers during food-restriction stress.

Corticosterone levels and ulcers were compared in vasopressin-containing (LE) and vasopressin-deficient (DI) rats under ad lib and food-restricted conditions. In the ad lib situation, DI and LE rats had similar corticosterone levels and no ulcers. After 1 day of food restriction, the corticosterone levels were elevated in DI and LE rats, with a significantly higher level in LE rats. No ulcers were present in either strain. After 2 days of food restriction, the corticosterone levels were similar in DI and LE rats. The level in DI rats was comparable to that of the preceding day, but the level in LE animals dropped significantly from the previous day. Significant ulceration was evident in DI rats, but absent in LE rats. Following 3 days of food restriction, the corticosterone level in LE rats had returned to the ad lib level, whereas, for DI rats, an elevated level was maintained. There were no ulcers in LE rats, but they were present in DI rats. Thus LE and DI rats responded differently to the stress of food restriction. The mechanism underlying the response is most likely related to changes in the hypothalamic-pituitary-adrenocortical axis and its reaction to stress.

Modulatory effects of vasopressin on glucose and protein metabolism during food-restriction stress.

Plasma levels of glucose and urea nitrogen were compared in vasopressin-containing (LE) and vasopressin-deficient (DI) rats under ad lib and food-restricted conditions. In the ad lib situation, DI and LE rats had similar levels of glucose and urea nitrogen. Variations in this pattern were observed under food-restricted conditions. The DI animals exhibited lower levels of glucose and higher levels of urea nitrogen than their LE counterparts. During food restriction, the glucose levels of LE animals were not different from that observed under ad lib conditions. A significant decrease, however, was observed in the glucose levels in DI animals during food restriction. Urea nitrogen levels in LE animals decreased during food restriction as compared to the ad lib situation, whereas urea nitrogen levels of DI animals increased during food restriction. These observations indicate that vasopressin has a modulatory role on glucose and protein metabolism during the stress of food restriction.

Vasopressin, immobilization, and the dexamethasone suppression test in rats.

To investigate the role of the hormone vasopressin (VP) in mediating the response of the body to stress, corticosterone levels of VP-containing (LE) rats and VP-deficient (DI) rats were compared following administration of the dexamethasone suppression test (DST) under stressed and nonstressed conditions. The stressor utilized was immobilization, an acute physical stressor. Dexamethasone (DEX), a synthetic glucocorticoid, was injected subcutaneously at a dose of 0.025 mg/kg. This dose of DEX was found to significantly suppress plasma corticosterone in the nonstressed animals (both DI and LE) via feedback inhibition of the hypothalamic-pituitary-adrenocortical (HPA) axis. In the stressed situation, however, LE animals exhibited "escape" from DEX suppression, whereas DI animals did not. Escape indicates a resistance of the HPA axis to the suppressive action of DEX. Thus, in the absence of corticotropin-releasing factor, which is inhibited by DEX, VP alone appears to be sufficient to elicit significant corticosterone release. These results support the hypothesis that VP plays an important role in the regulation of glucocorticoid release in acute stress via the HPA axis.

The interaction of vasopressin and the photic oscillator in circadian rhythms.

Telemetered body temperature (BT), heart rate (HR), and activity (AC) data were collected in vasopressin-containing Long-Evans (LE) and vasopressin-deficient Brattleboro (DI) rats. The rats were exposed to a 12/12 h light/dark cycle under three conditions: 1) ad lib feeding throughout the 24-h cycle, 2) two scheduled-feeding periods during the diurnal component of the light/dark cycle, and 3) two scheduled-feeding periods during the nocturnal component of the light/dark cycle. With ad lib feeding, natural nocturnal cycles of BT, HR, and AC were maintained in both strains. Marked changes were observed under the condition of scheduled feeding during the diurnal component of the light/dark cycle. In DI animals the influence of the photic oscillator was lost and BT, HR, and AC shifted from nocturnal to diurnal patterns. Circadian rhythms in DI animals were now synchronized by the nonphotic zeitgeber of scheduled food presentation. On the other hand, LE animals lost a well-defined circadian rhythmicity resulting from adherence to the photic oscillator, while at the same time being influenced by the nonphotic oscillator. Under the condition of scheduled feeding during the nocturnal component of the light/dark cycle, the circadian rhythms were similar in DI and LE rats. Results show that vasopressin has a significant interaction with the photic oscillator, which is obvious only when the photic and nonphotic oscillators are uncoupled. In addition, the results demonstrate that the strength of the photic oscillator is decreased or that the effect of this oscillator is masked or lost in DI rats compared to LE rats.

The role of vasopressin in modulating circadian rhythm responses to phase shifts.

Telemetered body temperature (BT), heart rate (HR), and motor activity (AC) data were collected in vasopressin-containing, Long-Evans (LE) and vasopressin-deficient, Brattleboro (DI) rats. In Experiment 1, the rats were initially exposed to a 12 h/12 h light/dark cycle under ad-libitum feeding and were then subjected to either a phase-advance or phase-delay shift of 6 h. After the phase-advance shift, neither strain adapted; however, after the phase-delay shift, both strains adapted rapidly. In Experiment 2, the animals were subjected to either a nocturnal or a diurnal restricted-feeding paradigm and were then exposed to either a phase-advance or phase-delay shift with synchronized feeding. In the nocturnal restricted-feeding paradigms, both strains rapidly adapted to both shifts. Concerning diurnal restricted-feeding, DI animals readily entrained to the presentation of food in both shifts; whereas, LE animals exhibited a confused rhythmicity. In Experiment 3, animals were subjected to a phase-advance shift, while the time of feeding was held constant. Following the shift, LE animals responded to the onset of the dark at the new time; yet, were still influenced by the presentation of food. The DI animals maintained the preshift circadian pattern and continued to be dominated by the presentation of food. These experiments indicate that circadian rhythms of LE animals are dominated by the light entrainable oscillator (LEO) in ad-libitum feeding and by both the LEO and food entrainable oscillator (FEO) in restricted-feeding. On the other hand, the circadian rhythms of DI animals are dominated by the FEO unless food is provided ad-libitum. The demonstrated role of vasopressin in synchronizing circadian rhythms to the LEO may be of significance in understanding human circadian rhythm disturbances, such as jet lag.

Interactions between vasopressin and food restriction on stress-induced analgesia.

To investigate the role of the hormone vasopressin (VP) in mediating the response of an organism to food restriction stress-induced analgesia, tail flick latencies and scored qualitative behavioral responses were recorded in VP-containing (LE) rats and VP-deficient (DI) rats. These variables were measured under nonstressed (ad lib) and stressed (food restriction) conditions. In the ad lib condition, DI and LE rats had a similar tail flick latency and scored qualitative behavioral response to the stimulus eliciting the tail flick. During the food restriction condition, however, LE animals developed significant food restriction stress-induced analgesia, as measured by tail flick latency. On the other hand, DI animals did not develop significant analgesia. In addition, DI animals exhibited a significantly greater scored qualitative behavioral response to the stimulus eliciting the tail flick than LE animals. These results demonstrate that VP plays an important role in the regulation of food restriction stress-induced analgesia, as well as the scored qualitative behavioral response elicited by the tail flick stimulus.

Vasopressin deficiency provides evidence for separate circadian oscillators of activity and temperature.

Vasopressin-containing Long-Evans and vasopressin-deficient Brattleboro rats were maintained in individual cages while telemetered activity (AC) and body temperature (BT) data were collected. Rats were initially exposed to a 12 h/12-h light/dark cycle (photic zeitgeber) and were allowed ad-libitum access to food and water. Daily feeding, care, and handling (nonphotic zeitgebers) occurred at the beginning of the second hour of the dark cycle. After a 14-day habituation period, rats were subjected to continuous light (LL) or dark (DD) and nonphotic cues were presented irregularly. During the habituation period, both strains exhibited clear 24-h circadian rhythms of AC and BT. In LL or DD, photic cues were removed and nonphotic cues were presented irregularly. There was a shift in the rhythm for Long-Evans animals to 26 h for both AC and BT in LL and 24.6 h in DD. Feeding, care, and handling were seen as minor artifact. In Brattleboro rats, although there were robust 26-h and 24.6-h circadian rhythms of AC in the LL and DD, respectively, BT data were inconsistent and showed sporadic fluctuations. In the BT rhythm of Brattleboro animals, strong peaks were associated with feeding, care, and handling times and trough periods were characterized by a dramatic drop in temperature. This experiment demonstrates that AC and BT are controlled by separate oscillators. In addition, the importance of vasopressinergic fibers in the control of circadian rhythms of BT is evidenced by the loss of circadian rhythms in animals lacking these functional fibers when exposed to free-running paradigms where there is no entrainment of photic or nonphotic oscillators.

Vasopressin deficiency and circadian rhythms during food-restriction stress.

Vasopressin-containing, Long-Evans (LE) rats and vasopressin-deficient, Brattleboro (DI) rats were monitored for activity and core body temperature via telemetry. Rats were exposed to a 12-12 light-dark cycle and allowed to habituate with ad lib access to food and water. The habituation period was followed by an experimental period of 23 h of food-restriction stress in which a 1-h feeding period was provided during the light cycle. Although both strains of animals showed nocturnal activity and temperature rhythms during the habituation period, DI rats were more active than LE rats. The DI rats also had a lower body temperature in the dark. During the experimental period, both strains exhibited a phase shift of activity and body temperature correlating with the presentation of food. The DI rats developed a diurnal shift more rapidly than LE rats. The DI animals showed a dramatic increase in activity during the light phase and a marked decrease in body temperature during the dark phase. The LE animals showed a significant attenuation of activity, but maintained both nocturnal and diurnal temperature peaks throughout the food-restricted condition.

Vasopressin deficiency and blood glucose interactions on passive avoidance behavior.

The performance of a passive avoidance task (measured for two trials based upon number of complete step-downs and latency to respond) and blood glucose levels were examined in five groups of animals. The groups included vasopressin-deficient (DI) and vasopressin-containing (LE) rats under ad lib (AL) and food-restricted (FR) conditions, as well as DI-FR animals provided with access to an 8% sucrose solution (SUC). In the AL condition, no significant differences were found between DI and LE animals in either step-down occurrences or blood glucose levels. However, the DI animals were significantly slower in latency to respond in trial 1. With FR, the LE animals resembled the LE-AL animals in both passive avoidance behavior and blood glucose levels. The DI-FR animals that were not provided with SUC showed an impairment in passive avoidance behavior and low blood glucose levels, whereas DI-FR animals provided with SUC showed an amelioration of passive avoidance deficiencies and had blood glucose levels comparable to AL animals and LE-FR animals. On trial 2, a significant negative correlation was found between number of step-down occurrences and blood glucose levels, and a significant positive correlation was found between latency to respond and blood glucose levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of TRH injection on hippocampal-hypothalamic-pituitary-thyroid interactions.

The first experiment was conducted in an attempt to ascertain the effects of hippocampal lesions on plasma levels of total T4, total T3, free T4, and TSH. Animals with hippocampal lesions had significantly lower levels of total T4, free T4 and TSH than cortical control and normal animals. There were no significant differences in total T3 among the three groups. Since these results indicated that animals with hippocampal lesions manifested a dysfunction in the hypothalamic-pituitary-thyroid axis, a second experiment was undertaken to determine the site of mediation. A TRH injection test demonstrated that the dysfunction occurs at the level of the hypothalamus. It is hypothesized that in the normal animal the hippocampus exerts a facilitating effect on the hypothalamic-pituitary-thyroid axis.

[Childhood drowning in the Netherlands]. / Verdrinking bij kinderen in Nederland.

OBJECTIVE: To investigate susceptible groups and risk factors for childhood drowning in the Netherlands with the aim of improving prevention campaigns. DESIGN: Prospective and partly retrospective. METHOD: Information about drowning accidents in 2010 and 2011 was collected using two methods. Firstly, drowning - with or without a fatal outcome - was added to the list of conditions to be reported to the Netherlands Paediatric Surveillance Unit (NSCK). Paediatricians received a comprehensive questionnaire when they had reported on drowning. Additional information on drowning was collected from online media (news websites and online journals). RESULTS: A total of 82 reports of drowning were analysed (63 from the paediatricians' survey and 19 additional reports from online media). Twenty-three children died as a result of drowning in the Netherlands in 2010 and 2011. Fifty-four percent of all cases of drowning were in children younger than 4 years. Boys were victims in 71% of the cases. Half (51%) of the accidents happened because the parents or caregivers lost sight of the children. In 27% of cases the accident took place in or around the home. Twenty-one children (26%) were victims of drowning in a public swimming pool and 5 of these children died. CONCLUSION: Better and continuous supervision of young children could help prevent more cases of drowning. Open water in proximity to the home should be fenced off. Continuous good supervision is also essential in public swimming pools.