1 Gastrointestinal Diseases Division, Communicable Disease Surveillance Centre, 61 Colindale Avenue, London NW9 5EQ, UK.
2 Infectious Disease Epidemiology Unit, Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Clarence C Tam, Gastrointestinal Diseases Division, Communicable Disease Surveillance Centre, 61 Colindale Avenue, London NW9 5EQ, UK. E-mail: ctam{at}phls.org.uk
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Abstract |
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Methods Data from a large study of IID in England were used to investigate factors influencing presentation to a general practitioner (GP) following an episode of IID. Multivariable logistic regression was performed, comparing GP presenters with non-presenters. Explanatory variables used were illness severity, recent foreign travel and socioeconomic indicators.
Results Severe illness (OR = 12.54, 95% CI: 7.5820.74), recent foreign travel (OR = 2.4, 95% CI: 1.394.14), leaving full-time education at an earlier age (OR = 2.06, 95% CI: 1.223.50) and housing categories representing lower socioeconomic status (SES) were all independently associated with GP presentation.
Conclusions Case reporting to national surveillance is shaped by complex biological and social factors, of which illness severity appears to be the most important. Results from case-control studies comparing cases of IID identified by surveillance with population controls are likely to generalize mainly to cases severe enough to be reported. Controlling for educational and SES (mostly housing) is required.
Accepted 19 July 2002
Surveillance systems provide convenient sources of cases for case-control studies of reportable infectious diseases comparing reported cases with population controls in terms of exposureto pertinent risk factors. However, the completeness of surveillance systems varies by disease. In the UK, it is estimated that one out of 136 cases of infectious intestinal disease (IID) is reported.1 To be reported to a surveillance system, a case must present to a healthcare facility, their general practitioner (GP) must request and submit a stool specimen and an organism must be identified (Figure 1). Thus, reported cases are likelyto differ systematically from unreported cases. If reporting is related to factors such as disease severity, and these are, in turn, associated with exposure, results from studies using only reported cases will not be generalizable to all cases. The comparability of these cases with population controls has also been questioned, since the latter do not undergo an equivalent selection process.2 Factors influencing the reporting of cases will, therefore, introduce biases if they are associated with the exposures under investigation. In this analysis, data from a large study of IID in England3 were used to investigate factors associated with presentation to general practice, the first stage in the selection of reported cases.
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Materials and Methods |
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To be reported to national surveillance an individual with IID must first present to the health services. Factors influencing likelihood of GP consultation might, therefore, affect the representativeness of reported cases. In this analysis, data obtained from cases identified in the community cohort and GP components of the IID study were used to identify factors associated with GP presentation.
Cases identified in the IID study for whom a completed exposure questionnaire was available were included in the analysis. Cases were defined as persons with loose stools or significant vomiting lasting <2 weeks, in the absence of a known non-infectious cause and preceded by a symptom-free period of 3 weeks. Vomiting was considered significant if it occurred more than once in a 24-hour period and if it incapacitated the case or was accompanied by other symptoms such as cramps or fever.3 Several socio-demographic indicators, symptom profile and detailed exposure history for the 10 days prior to illness onset were available for each case. All were asked if they had consulted their GP for their illness. The analysis was restricted to those aged 16 years. Information on cases <16 years was obtained by proxy from a parent or guardian using a questionnaire specific for this age group. The GP presentation patterns are also likely to be different for children. A separate analysis of relevant factors in this age group is, therefore, required but not presented here.
The analysis compared all cases presenting to the GP (GP cases and cohort cases who presented to the GP) with cases ascertained in the cohort who did not present to a GP (Figure 1). Grouping all GP presenters was acceptable as community GP presenters and GP cases were similar in terms of socio-demographic and other variables considered.
Factors considered to be potentially associated with GP presentation were socio-demographic characteristics, recent foreign travel, recent similar symptoms in household members and severity of illness. The socio-demographic variables considered included age, gender, marital status, employment status, social class, partners social class, age at leaving full-time education, type of accommodation, ownership versus rental of accommodation, number of rooms in the house, and sharing bathroom and kitchen facilities with people other than household members. Social class was categorized on a decreasing scale from I to V based on patients occupation according to the Office of Population Censuses and Surveys Standard Occupational Classification.5
For disease severity, the presence, duration and self-reported severity of 15 different IID-associated symptoms were scored for each patient (Table 1). In order to obtain an overall severity score for every patient, presence, duration and severity scores for each symptom were multiplied and the product scores summed across all symptoms. The distribution of severity scores was highly positively skewed, and scores were grouped into mild, moderate and severe using the 33rd and 66th percentiles of the distribution as cut-off points.
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Multivariable analysis
Variables associated with GP presentation at the 0.1 significance level in the single variable analysis were included in a multivariable logistic regression analysis. Correlations between explanatory variables were assessed using a correlation matrix. For highly correlated variables (r > 0.8 as suggested by Katz)7, only the variable that was most strongly associated with GP presentation in the single variable analysis was included in the multivariable models. The correlation matrix is available from the authors on request.
A backwards elimination multivariable model was constructed including firstly the outcome and the candidate explanatory variables. Age and gender were retained as potential confounders in all models. Variables were removed from the model one by one, beginning with the most weakly associated, based on their confounding effect and their contribution to the model as assessed by the likelihood ratio (LR) test. Variables whose removal from the model caused large fluctuations in OR (>10%) were retained, as were variables whose removal gave rise to significant LR tests (P < 0.05). Variables were removed successively until all remaining variables fulfilled the criteria for inclusion.
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Results |
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Cohort cases presenting to the GP differed in age structure from GP cases: there was a lower proportion of under 45s in the cohort compared with the GP group (2 = 14.83, P = 0.011). This was expected, since the age distribution in the cohort component of the IID study was known to differ from that in the GP component.3 No significant differences were found in the remaining variables and the two groups were combined for subsequent analyses.
In the single variable analysis, working part-time (versus full-time) reduced the likelihood of GP presentation (Table 2). The GP presenters were more likely to have left full-time education at a younger age; be single or widowed; be in a lower social class (III-Manual or V); have a partner in a lower social class (III-Manual or IV); live in accommodation other than a detached or semi-detached house; rent as opposed to own their accommodation; live in a residence with fewer rooms; and share kitchen or bathroom facilities with people other than members of their household. In addition, GP presenters had more severe disease and were more likely to have travelled abroad shortly before their illness.
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In the final multivariable model adjusting for age and gender, cases leaving full-time education before the age of 16 were twice as likely as those leaving at age 19 to present to their GP for an episode of IID (Table 3
). Living in a terraced house or rooms in a converted house and living in purpose-built flat or maisonette were associated with an increased likelihood of GP presentation compared with living in a detached or semi-detached house. In addition, those living in privately-rented accommodation were more likely to present to their GP than those living in owned or mortgaged property. Foreign travel was strongly associated with GP presentation, with those travelling abroad in the 10 days prior to illness being more likely to seek medical advice than those not travelling abroad.
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The effect of socioeconomic variables by degree of illness severity was also investigated. The results suggested that the effect of age at leaving education on GP presentation was more marked among mild cases, while the effect of living in rented accommodation was greater among severe cases (data not shown). However, the numbers in each category were not sufficient to confidently discount random variation.
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Discussion |
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Cases who left full-time education before the age of 16 were more likely to present to their GP for an episode of IID than those who left full-time education at age 19 years. Educational level may influence an individuals health beliefs and awareness of health-related issues, considered an important predisposing factor for healthcare usage.8 Health beliefs may also shape an individuals perception of health status and, hence, need for healthcare.8 Individuals with a longer period of full-time education might be better able to judge the severity of their illness or be more aware of how to manage it, with a smaller proportion thus feeling the need for GP consultation.
Housing categories broadly representing decreasing socioeconomic status (SES) were associated with an increased likelihood of GP presentation. Living in rented accommodation and lower social class have been associated with higher rates of GP utilization.911 Social class was not found to be significantly associated with GP presentation after adjustment for other socioeconomic variables, suggesting that housing and education variables are more relevant indicators of GP presentation patterns.
A GP presentation was more likely among cases who had recently travelled abroad even after controlling for severity, indicating that travel-associated cases are over-represented in national surveillance systems, and that the contribution of foreign travel to IID is likely to be overestimated in case-control studies using reported cases.
After adjusting for other variables, the strongest predictor of GP presentation for IID was the severity of illness. This supports findings from a similar study in The Netherlands, in which more severe symptoms, particularly fever and abdominal pain, were associated with GP presentation.12 This indicates that cases of IID identified by national surveillance represent those at the more severe end of the clinical spectrum. Reported cases thus also differ from all cases in terms of the distribution of causative agents, since pathogens causing more severe disease are more likely to be reported.3 This has implications for the conduct of case-control studies. For pathogens in which severity is associated with particular risk factors (for example, if a route of transmission leads to ingestion of higher numbers of the pathogen, and this causes more severe illness), the use of reported and thus more severe cases would identify factors associated with severe but not mild disease.
It is likely that a complex interplay exists between social and biological factors. For example, the extent to which SES plays a role in determining a persons likelihood of seeking medical attention might depend upon illness severity, such that those with severe illness might present to their GP regardless of their socioeconomic background. This can be investigated by estimating the effect of SES for each category of disease severity, but in this analysis numbers were insufficient to provide conclusive results.
In addition to factors associated with GP presentation, the selection of reported cases will be influenced by stages further up the reporting chain. Of particular interest would be understanding what influences physicians to request stool specimens from patients with suspected IID. This might include clinical presentation, occupation, age, co-morbidity and knowledge of risk factors such as recent consumption of high-risk foods or travel to a high-risk area. The GPs own attitudes may also play a role, although these are difficult to quantify.
Further up the reporting pyramid, a certain proportion of GP-submitted stool samples will be positive for IID-associated pathogens. The detection of an organism will depend on the timing and quality of the sample and the investigation criteria and detection methods used by the laboratory. Many gastrointestinal pathogens are not routinely screened for, unless warranted by the clinical or epidemiological circumstances. These vary by organism, but positive specimens for non-routine organisms are likely to be biased towards cases with more severe clinical presentation, susceptible age groups, patients with underlying immunodeficiency, cases with suspected risk factors for the organism, such as consumption of specific foods or recent travel to a high risk area, and outbreak-related cases. If the microbiological investigation of a case of IID is influenced by suspicion of exposure to certain risk factors, results from case-control studies will be biased towards the identification of these factors, and this will perpetuate (perhaps spurious) knowledge of their importance. In order to avoid these potential biases the organism of interest should be screened for in all stool specimens submitted using standard procedures in all collaborating laboratories. This may require additional funds and resources.
In the final stage of the reporting process, a proportion of positive specimens is reported to national surveillance. Here, completeness of reporting may favour outbreak-related cases. Where a case-control study is not being carried out as part of an outbreak investigation, cases from known large-scale outbreaks should be excluded in order to prevent the results being distorted by a single, unusual event.
This analysis provides evidence that following an episode of IID, the principal factor influencing GP presentation is severity of illness, and that this is likely to affect the generalizability of results from case-control studies using reported cases. Foreign travel in the weeks before the illness also influences presentation, apparently unrelated to severity of illness, and this may well be related to perceptions of causation of the illness. The data also suggest that factors not related to the illness (education and housing) can influence presentation. This indicates that population controls are not representative of the population from which reported cases arise. It is possible to adjust for a biased selection of controls where the distribution of factors affecting selection is known13 and this analysis suggests that education and living conditions should be controlled for. Alternatives to population controls have been proposed, including the use of casecase comparisons to avoid potential biases introduced through the reporting process.2 This involves comparing subgroups of cases with the same disease (e.g. salmonellosis) but differing subtype aetiologies (e.g. Salmonella Enteritidis versus Salmonella Typhimurium). In this approach, risk factors that are common to both subgroups are effectively matched for, so that only risk factors differing between the subgroups are investigated. It has the advantage that subtype-specific risk factors can be investigated in a timely fashion without the additional expenditure and resources required to recruit controls. However, differences in the distribution of illness severity, foreign travel, SES or other factors between the subgroups being compared could make the approach prone to the same problems as the conventional case-control design, since differences in GP presentation and, hence, case selection will still occur. An option for case-control studies might be to perform the analysis separately for different categories of disease severity. If severity is indeed associated with risk factors of interest, any bias due to underascertainment would be expected to affect mild cases in particular, since these are less likely to be reported, while results for severe cases should be more representative of severe cases in the population.
Surveillance mechanisms provide convenient sources of cases for studies of risk factors for infectious intestinal diseases. Although such cases may not be an ideal sampling frame for cases, alternative approaches are not always suitable, since for many IID-associated pathogens full characterization may only be performed at a national microbiological reference centre. From an epidemiological perspective, the importance of illness severity is reassuring, since it indicates that following an episode of IID, the main influence on the likelihood of GP presentation is severe illness. The choice of population controls introduces an additional bias, as presentation is also influenced by foreign travel and SES. Examination of the individual stages involved in the reporting of cases of IID to national surveillance reveals a complex series of biological, social and operational factors that shape the characteristics of reported cases. The interpretation of results from case-control studies using reported cases and population controls is, therefore, not straightforward, but likely to be robust if analysis controlling for educational and socioeconomic variables is performed, and to extend to those cases severe enough to be reported to national surveillance.
KEY MESSAGES
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Acknowledgments |
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Notes |
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PJ Roderick, LC Rodrigues, B Rowe, D Sethi, HR Smith, MT Skinner, R Skinner, PN Sockett, DS Tompkins, PG Wall, JG Wheeler, AL Wight.
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