Case-control studies are the traditional ways in which foodborne enteric diseases are studied and outbreaks are investigated. This method has some significant limitations and biases for diseases with low efficiency reporting rates, such as Campylobacter, a common foodborne disease. Case-case methodologies have been explored for these studies but have been implemented without any clear strategy. This dissertation aims to first, determine the common risk factors for Campylobacter in Arizona using the traditional case-control study design, second, to systematically compare case-case studies to the more common case-control studies, and third, to simultaneously compare the results of a community outbreak of Campylobacter using both case-control and case-case study designs. Results from these studies identified some unique risk factors for routine Campylobacter infection in Arizona that will be used to enhance surveillance for the disease in the state. A systematic review of case-case studies used for enteric diseases found that there are specific recommendations that can be put into place in determining what comparison cases should be selected based on the primary aims and goals of the study. Finally, the results of the simultaneous case-case and case-control studies of a Campylobacter outbreak showed that these methods may work best in conjunction with one another and in doing so, the most accurate depiction of the source of infection can be determined.

No description available.

Master of Science / Department of Diagnostic Medicine/Pathobiology / Richard Hesse / Bovine Coronavirus (BCoV) is known to cause enteric and respiratory diseases, such as calf diarrhea, winter dysentery, calf respiratory disease, and bovine respiratory disease complex (BRD). All of these diseases are believed to be caused by the same genotype of BCoV. BCoV exhibits tissue tropism for both the gastrointestinal and respiratory tracts. This tropism is due to 9-O-acetylated sialic acid receptor on both epithelial cells in the respiratory and enteric tract. Currently, the only vaccine available for BCoV targets the enteric form of the disease. This study addresses the hypothesis that antibodies from the enteric form of the disease can cross neutralize the respiratory form of the virus. Data from surveillance studies suggest that BCoV is one of the major contributors to BRD, for which there is no currently approved vaccine for the respiratory form of the disease. Our approach to answering this question is to sequence and analyze the complete genome of 11 respiratory and enteric coronavirus isolates using next generation sequencing (NGS). Following the NGS, viruses were selected based on phylogenetic analysis and ability to grow and be maintained in cell culture. These viruses were then be used as serum neutralization indicator viruses in SN assays. 147 bovine serums submitted to KSVDL were used to determine if there are any serological differences between the immune response to respiratory versus enteric viruses based on the antibodies produced by the animal. The overall results show that there are few differences between the enteric and respiratory isolates at the genomic level and the serological response from the animal to these viruses. The differences between enteric and respiratory virus will need to be further addressed and analyzed to conclude if there is a noteworthy difference between the viruses with different tropisms. Other factors, such as host immune response and environment, are believed to be involved in the virus tropism to certain areas of the body.

Background: An estimated 1.27 million people per year are experiencing acute gastrointestinal illness (AGI) due to private water sources, which are federally unregulated drinking water sources in the US (Murphy et al., 2017). Previous studies have found a relationship between drinking water source (domestic well or publicly supplied water) and waterborne disease. Although some work has been done to characterize the quality of water in karstic terrain, and karst is considered to be a risk factor for pathogenic contamination of domestic wells, little work has been done to assess the relationship between karst and incidence of enteric disease. There is also little known about the socio-demographic factors of populations in the US using domestic wells. Although studies have also shown an association between rain, antecedent rain, and waterborne illness, the relationship is not well defined. Objective: The dissertation uses spatiotemporal and epidemiologic methods to characterize domestic well users in Pennsylvania, determine the relationship between use of domestic wells and cases of illness, and investigate an interactive effect between rain and drought on county level occurrence of reporting of illness. This work includes illness due to Salmonella, Campylobacter, Giardia, and Cryptosporidium as reported to the PA department of health. The population of interest is the estimated 12.8 million people who lived in PA from 2010-2019, of which an estimated 3.5 million used a domestic well. Aim 1: Determine whether populations of Pennsylvania that rely on domestic wells are more socially vulnerable than those with access to public water supply or wastewater treatment. Hypothesis: Census tracts that are generally more socially vulnerable are also more likely to lack access to public water supply. Aim 2: Determine presence of spatial clusters of reportable enteric diseases (Salmonella, Campylobacter, Giardia, or Cryptosporidium) between 2010 and 2019 in PA, and whether those clusters are associated with drinking water source (whether a domestic well or publicly supplied water). Hypothesis 1: Enteric disease in PA for the 2014 - 2018 time period cluster in time and space. Hypothesis 2: The incidence risk ratio of reported enteric disease will be positively associated with the proportion of households utilizing domestic wells. Aim 3: Determine the effects of rain and drought on weekly counts of reportable enteric illness (Salmonella, Campylobacter, Giardia, or Cryptosporidium) in PA, 2010-2019. Hypothesis 1: County level weekly enteric illness incidence rates are positively associated with total rain (cm) in prior week(s). Hypothesis 2: The incidence rate of reportable enteric illness by county is associated with an interaction between total rain (cm) in the prior week by county and drought conditions as measured by the Palmer Drought Severity Index in the same week the rain is measured preceding disease onset. Methods: Using county and zip code tabulation area incidence data on enteric illnesses made available from the Pennsylvania Department of Health for the years 2010 to 2019, this thesis investigated the potential relationships between rain, drought conditions, use of private wells, and the occurrence of karstic terrain and illness. The social characteristics of those who do not have access to public water supply were also explored. This was done in three parts, all utilizing ecologic study designs. Aim 1: We assessed how social vulnerability measures co-occur with domestic well use and also how those patterns change over space using a profile regression method. Aim 2: We examined the spatial patterns, by Zip Code Tabulation Area using a Poisson Spatial only SaTScan analysis with 5% of the state population without Philadelphia allowing for hierarchical clusters, and temporal patterns, using the R software trending package to develop a season adjusted negative binomial model to assess outbreaks, of weekly reported enteric illnesses. The weekly county incidence rates for each illness were also assessed by percentage of a county that did not have access to public water supply and presence of karst using a zero-inflated negative binomial model with random intercept for county. Philadelphia was excluded because they did not share their data. To assess the second hypothesis, that the incidence risk ratio of reported enteric disease is positively associated with the proportion of households utilizing domestic wells, a zero-inflated negative binomial model with a random intercept for county was utilized to determine if there was an association. This same model was expanded as assessment of an association between illness rates and percentage of a county underlain by karst. Aim 3: We assessed multiple time lags using a zero-inflated negative binomial model with random intercept for county to determine if there was an relationship between county level weekly rainfall (cm) and drought, as measured by the Palmer Drought Severity Index, on the weekly incidence rates of these four reportable enteric illnesses. Philadelphia was excluded, because they did not share their data. If both the amount of rain and the level of drought were found to be related to the number of cases of illnesses, an interaction was assessed for that lag time.Results: Aim 1: Measures of social vulnerability have 15 distinct profiles or clusters in the state of PA. These clusters occur spatially heterogeneously across the state. Five distinct population-profiles are more likely to rely on a domestic well. Two of these profiles are also more likely to experience social vulnerability when measured at the census tract level. In general, census tracts with higher proportions of homeowners, lower proportions of those without a high school diploma, lower median per capita income, and higher proportions of children under the age of 5 and 17 are more likely to rely on an unregulated drinking water source than populations with greater proportions of their population having a high school diploma, higher median per capita income and lower proportions of their population consisting of people under the age of 5 and 17. Aim 2: All four pathogens, which were assessed, have spatial heterogeneity in the state of Pennsylvania. All pathogens had higher incidence rates in the summer and lowest rates in the winter. However, most outbreaks occurred in the wintertime. A positive association was found between quartile of area of a county not served by public water supply and incidence rates of campylobacteriosis [IRR = 1.35 (95%CI 1.21, 1.51 p < 0.001)], cryptosporidiosis [IRR = 1.33 (95%CI 1.07, 1.66, p < 0.05)], and giardiasis [IRR = 1.25 (95%CI 1.11, 1.42, p < 0.01)]. An association was also observed between the quartile of area of a underlain by karst and incidence rates of campylobacteriosis [IRR = 1.21 (95%CI 1.08, 1.35, p <0.01)] and cryptosporidiosis [IRR = 1.36 (95%CI 1.09, 1.69, p < 0.01)]. Aim 3: There was at least one lag time (weeks between weekly measure of rain and specimen collection) where the amount of rain was positively associated with counts of campylobacteriosis, salmonellosis, and giardiasis. We also evaluated potential associations between enteric disease and rain as well as previous drought conditions (wetness or lack thereof) with various time-lags for 66 counties of PA for a 10-year time, Philadelphia is not included in this analysis because their data was not shared. In the case of Salmonella, there were four different lag times with an increase in incidence (weeks 4, 5, 11 and 12) and Giardia had two different lag times that showed an increase in incidence (weeks 12, and 14 ). At week 11 for cases due to Campylobacter, there was also an assessed interaction, while both rain and drought, as measured by the weekly Palmer Drought Index (PDI) had a positive relationship with risk, the relationship changed direction and was protective [IRR = 0.9997 (95%CI 0.9997, 0.9999, p < 0.01)]. Conclusions: The key findings are: 1. There are distinct profiles of domestic well users that differ by measures of social vulnerability. Two types of census tracts in PA are likely to have a high number of domestic wells and experience high social vulnerability traits. 2. Enteric illnesses due to Salmonella, Campylobacter, Giardia and Cryptosporidium, have patterns of clustering spatially across the state, and have a strong relationship with season. 3. There is a positive association between the area of a county not served by public water supply and incidence rates of campylobacteriosis, cryptosporidiosis, and giardiasis. 4. There is a positive association between the area of a county underlain by karst and incidence rates of campylobacteriosis and cryptosporidiosis. 5. That rain and drought (wetness) conditions weeks to several weeks prior, affect the incidence rate ratio of cases of Giardia, Cryptosporidium, Campylobacter, and Salmonella in Pennsylvania. The relationship between rain and drought conditions and illness varies by organism type which could be attributed to incubation period, reporting time, transport time in the environment and exposure sources (drinking water, food, recreation). There was evidence of an interactive effect between rain and drought conditions for cases of campylobacteriosis, with an 11-week lag time. / Epidemiology

Mandatory notification of disease forms the backbone of disease surveillance in New Zealand and overseas. Notification data is used by public health professionals and academics to identify cases requiring public health control, monitor disease incidence and distribution, and in epidemiological research. However, there is emerging evidence that notification rates do not accurately reflect the true extent of notifiable diseases within the community, resulting in the underascertainment of many notifiable cases. While adequate surveillance does not necessarily require that all cases of notifiable disease be captured, the systematic underascertainment of disease can have significant implications for perceived spatial and demographic trends in disease prevalence; potentially threatening the credibility of spatial epidemiological research by under or overestimating the burden of disease in different populations. There is evidence that systematic underascertainment occurs as a result of the differential actions of laboratories and general practitioners. It has also been recognised that that underascertainment can be influenced by a patient's willingness to seek medical attention and participate in laboratory tests. However, few studies have investigated whether these factors systematically influence notification either in New Zealand or overseas. Furthermore, the discipline of health geography has been slow to engage with this topic of public health importance, despite the inherently spatial nature of the processes involved, and the close ties to the geographic literature on health service utilization and healthcare provision. This thesis explores the spatial and temporal variation in notification rates in New Zealand for the period 1997-2005 and the potential relationships between notification rates and different variables. Unlike many underascertainment studies, which have used individual data and capture-recapture methods, data constraints inspired a unique ecological approach to investigating the factors which may be associated with notification in New Zealand. Variables were divided into categories based on Anderson's behavioural model for healthcare utilization and the influence of these variables on notification was determined through multiple regression analyses. The main findings of this research indicate that in New Zealand notification rates have increased during the period 1997-2005 and that there is a north-south gradient in notifications, with substantially lower rates in the North Island than in the South Island. Furthermore, it is also evident that the variables associated with notification vary according to disease, spatial aggregation and spatial scale. Notification rates are significantly associated with a range of predisposing and enabling factors which might influence patient choice to consult for many frequently underascertained diseases. More variation in enteric diseases is explained by the independent variables analysed than the variation in non-enteric diseases. However, further research into these relationships, and underascertainment in general, is required before firm conclusions can be drawn.

An enhanced notified enteric disease surveillance trial began on 1 July 2007 and continued until 30 June 2008. The aim of the trial was to measure the quality, timeliness and completeness of data collected and submitted by a regional Public Health Service (PHS) to the Institute of Environmental Science and Research Limited (ESR), via the national disease database (EpiSurv) for notified cases of enteric diseases. The trial evaluated two different methods of data collection: postal questionnaires and telephone interviews. Telephone interview techniques were used to improve the contact rate, timeliness and completeness of data gathered from all notified cases of campylobacteriosis in the Manawatu, Horowhenua and Tararua regions. The target set for the project was to achieve a 95% contact rate with 90% full completion of all EpiSurv data fields. For all notified cases of campylobacteriosis a 97% contact rate was achieved in a time frame of between zero to 20 days (three day median) and completeness of all the EpiSurv case report fields ranged between 96 – 100% in the final data. Prior to the commencement of the study, between 1 July 2004 to 30 June 2005, MidCentral PHS (MCPHS) made contact with around 58% of all notified cases of campylobacteriosis and 77% of all other notified enteric disease cases1 . A short pre-screen mail questionnaire, with reply-paid envelope, was sent to all notified cases of cryptosporidiosis, giardiasis, salmonellosis and yersiniosis in the MCPHS regions. EpiSurv case report fields were completed using information supplied in the returned questionnaires. Return rate, timeliness, and completeness were compared with the telephone interview group. Fifty three percent of cases we attempted to contact via mail questionnaire responded within two to 63 days (six day median) and completeness of all the EpiSurv case report fields ranged between 81 – 100%. In addition, we monitored the newly introduced ESR Early Aberration Reporting System (EARS) flags for increased levels of disease compared to historical disease rates, and assessed its usefulness as a tool to identify potential outbreaks in the region. While no outbreaks that had not already been identified by PHS staff were found by monitoring the EARS system, EARS has become an important tool in the MCPHS for comparing our rates of disease with bordering PHSs. EARS also provided a good quick reference tool for media enquiries and the graphs produced in EARS have been well utilised as visual aids for training and seminars presented during the trial period. The results of the surveillance trial initiatives were compared to the rest of New Zealand (NZ) over the same time frame and with a comparable, medium-sized, PHS. While the results of the telephone interviews from the MCPHS trial were close to the comparable PHS, they were significantly higher than for the rest of NZ. The postal questionnaires achieved a lower contact rate than the comparable PHS but similar to the rest of NZ. However, the quality of data gathered in the returned MCPHS postal questionnaire was significantly higher in most fields. Additional analysis was undertaken which indicated that those cases living in higher deprivation and rural areas were less likely to respond to a postal questionnaire. An over-representation of common enteric disease notifications from rural areas in the MCPHS was also highlighted by our research. This trial has shown the effectiveness of utilising telephone interviews and telemarketing techniques for gathering timely and complete data for human enteric disease surveillance within the MCPHS. It has also demonstrated that a short pre-screen questionnaire can be effective in collecting good quality data needed to complete the standard EpiSurv case report form.

An enhanced notified enteric disease surveillance trial began on 1 July 2007 and continued until 30 June 2008. The aim of the trial was to measure the quality, timeliness and completeness of data collected and submitted by a regional Public Health Service (PHS) to the Institute of Environmental Science and Research Limited (ESR), via the national disease database (EpiSurv) for notified cases of enteric diseases. The trial evaluated two different methods of data collection: postal questionnaires and telephone interviews. Telephone interview techniques were used to improve the contact rate, timeliness and completeness of data gathered from all notified cases of campylobacteriosis in the Manawatu, Horowhenua and Tararua regions. The target set for the project was to achieve a 95% contact rate with 90% full completion of all EpiSurv data fields. For all notified cases of campylobacteriosis a 97% contact rate was achieved in a time frame of between zero to 20 days (three day median) and completeness of all the EpiSurv case report fields ranged between 96 – 100% in the final data. Prior to the commencement of the study, between 1 July 2004 to 30 June 2005, MidCentral PHS (MCPHS) made contact with around 58% of all notified cases of campylobacteriosis and 77% of all other notified enteric disease cases1 . A short pre-screen mail questionnaire, with reply-paid envelope, was sent to all notified cases of cryptosporidiosis, giardiasis, salmonellosis and yersiniosis in the MCPHS regions. EpiSurv case report fields were completed using information supplied in the returned questionnaires. Return rate, timeliness, and completeness were compared with the telephone interview group. Fifty three percent of cases we attempted to contact via mail questionnaire responded within two to 63 days (six day median) and completeness of all the EpiSurv case report fields ranged between 81 – 100%. In addition, we monitored the newly introduced ESR Early Aberration Reporting System (EARS) flags for increased levels of disease compared to historical disease rates, and assessed its usefulness as a tool to identify potential outbreaks in the region. While no outbreaks that had not already been identified by PHS staff were found by monitoring the EARS system, EARS has become an important tool in the MCPHS for comparing our rates of disease with bordering PHSs. EARS also provided a good quick reference tool for media enquiries and the graphs produced in EARS have been well utilised as visual aids for training and seminars presented during the trial period. The results of the surveillance trial initiatives were compared to the rest of New Zealand (NZ) over the same time frame and with a comparable, medium-sized, PHS. While the results of the telephone interviews from the MCPHS trial were close to the comparable PHS, they were significantly higher than for the rest of NZ. The postal questionnaires achieved a lower contact rate than the comparable PHS but similar to the rest of NZ. However, the quality of data gathered in the returned MCPHS postal questionnaire was significantly higher in most fields. Additional analysis was undertaken which indicated that those cases living in higher deprivation and rural areas were less likely to respond to a postal questionnaire. An over-representation of common enteric disease notifications from rural areas in the MCPHS was also highlighted by our research. This trial has shown the effectiveness of utilising telephone interviews and telemarketing techniques for gathering timely and complete data for human enteric disease surveillance within the MCPHS. It has also demonstrated that a short pre-screen questionnaire can be effective in collecting good quality data needed to complete the standard EpiSurv case report form.

An enhanced notified enteric disease surveillance trial began on 1 July 2007 and continued until 30 June 2008. The aim of the trial was to measure the quality, timeliness and completeness of data collected and submitted by a regional Public Health Service (PHS) to the Institute of Environmental Science and Research Limited (ESR), via the national disease database (EpiSurv) for notified cases of enteric diseases. The trial evaluated two different methods of data collection: postal questionnaires and telephone interviews. Telephone interview techniques were used to improve the contact rate, timeliness and completeness of data gathered from all notified cases of campylobacteriosis in the Manawatu, Horowhenua and Tararua regions. The target set for the project was to achieve a 95% contact rate with 90% full completion of all EpiSurv data fields. For all notified cases of campylobacteriosis a 97% contact rate was achieved in a time frame of between zero to 20 days (three day median) and completeness of all the EpiSurv case report fields ranged between 96 – 100% in the final data. Prior to the commencement of the study, between 1 July 2004 to 30 June 2005, MidCentral PHS (MCPHS) made contact with around 58% of all notified cases of campylobacteriosis and 77% of all other notified enteric disease cases1 . A short pre-screen mail questionnaire, with reply-paid envelope, was sent to all notified cases of cryptosporidiosis, giardiasis, salmonellosis and yersiniosis in the MCPHS regions. EpiSurv case report fields were completed using information supplied in the returned questionnaires. Return rate, timeliness, and completeness were compared with the telephone interview group. Fifty three percent of cases we attempted to contact via mail questionnaire responded within two to 63 days (six day median) and completeness of all the EpiSurv case report fields ranged between 81 – 100%. In addition, we monitored the newly introduced ESR Early Aberration Reporting System (EARS) flags for increased levels of disease compared to historical disease rates, and assessed its usefulness as a tool to identify potential outbreaks in the region. While no outbreaks that had not already been identified by PHS staff were found by monitoring the EARS system, EARS has become an important tool in the MCPHS for comparing our rates of disease with bordering PHSs. EARS also provided a good quick reference tool for media enquiries and the graphs produced in EARS have been well utilised as visual aids for training and seminars presented during the trial period. The results of the surveillance trial initiatives were compared to the rest of New Zealand (NZ) over the same time frame and with a comparable, medium-sized, PHS. While the results of the telephone interviews from the MCPHS trial were close to the comparable PHS, they were significantly higher than for the rest of NZ. The postal questionnaires achieved a lower contact rate than the comparable PHS but similar to the rest of NZ. However, the quality of data gathered in the returned MCPHS postal questionnaire was significantly higher in most fields. Additional analysis was undertaken which indicated that those cases living in higher deprivation and rural areas were less likely to respond to a postal questionnaire. An over-representation of common enteric disease notifications from rural areas in the MCPHS was also highlighted by our research. This trial has shown the effectiveness of utilising telephone interviews and telemarketing techniques for gathering timely and complete data for human enteric disease surveillance within the MCPHS. It has also demonstrated that a short pre-screen questionnaire can be effective in collecting good quality data needed to complete the standard EpiSurv case report form.

Mandatory notification of disease forms the backbone of disease surveillance in New Zealand and overseas. Notification data is used by public health professionals and academics to identify cases requiring public health control, monitor disease incidence and distribution, and in epidemiological research. However, there is emerging evidence that notification rates do not accurately reflect the true extent of notifiable diseases within the community, resulting in the underascertainment of many notifiable cases. While adequate surveillance does not necessarily require that all cases of notifiable disease be captured, the systematic underascertainment of disease can have significant implications for perceived spatial and demographic trends in disease prevalence; potentially threatening the credibility of spatial epidemiological research by under or overestimating the burden of disease in different populations. There is evidence that systematic underascertainment occurs as a result of the differential actions of laboratories and general practitioners. It has also been recognised that that underascertainment can be influenced by a patient's willingness to seek medical attention and participate in laboratory tests. However, few studies have investigated whether these factors systematically influence notification either in New Zealand or overseas. Furthermore, the discipline of health geography has been slow to engage with this topic of public health importance, despite the inherently spatial nature of the processes involved, and the close ties to the geographic literature on health service utilization and healthcare provision. This thesis explores the spatial and temporal variation in notification rates in New Zealand for the period 1997-2005 and the potential relationships between notification rates and different variables. Unlike many underascertainment studies, which have used individual data and capture-recapture methods, data constraints inspired a unique ecological approach to investigating the factors which may be associated with notification in New Zealand. Variables were divided into categories based on Anderson's behavioural model for healthcare utilization and the influence of these variables on notification was determined through multiple regression analyses. The main findings of this research indicate that in New Zealand notification rates have increased during the period 1997-2005 and that there is a north-south gradient in notifications, with substantially lower rates in the North Island than in the South Island. Furthermore, it is also evident that the variables associated with notification vary according to disease, spatial aggregation and spatial scale. Notification rates are significantly associated with a range of predisposing and enabling factors which might influence patient choice to consult for many frequently underascertained diseases. More variation in enteric diseases is explained by the independent variables analysed than the variation in non-enteric diseases. However, further research into these relationships, and underascertainment in general, is required before firm conclusions can be drawn.

No description available.