A multi-level approach for investigating socio-economic and agricultural risk factors associated with rates of reported cases of Escherichia coli O157 in humans in Alberta, Canada.

Using negative binomial and multi-level Poisson models, the authors determined the statistical significance of agricultural and socio-economic risk factors for rates of reported disease associated with Escherichia coli O157 in census subdivisions (CSDs) in Alberta, Canada, 2000-2002. Variables relating to population stability, aboriginal composition of the CSDs, and the economic relationship between CSDs and urban centres were significant risk factors. The percentage of individuals living in low-income households was not a statistically significant risk factor for rates of disease. The statistical significance of cattle density, recorded at a higher geographical level, depended on the method used to correct for overdispersion, the number of levels included in the multi-level models, and the choice of using all reported cases or only sporadic cases. Our results highlight the importance of local socio-economic risk factors in determining rates of disease associated with E. coli O157, but their relationship with individual risk factors requires further evaluation.

Epidemiological characteristics of reported sporadic and outbreak cases of E. coli O157 in people from Alberta, Canada (2000-2002): methodological challenges of comparing clustered to unclustered data.

Using multivariable models, we compared whether there were significant differences between reported outbreak and sporadic cases in terms of their sex, age, and mode and site of disease transmission. We also determined the potential role of administrative, temporal, and spatial factors within these models. We compared a variety of approaches to account for clustering of cases in outbreaks including weighted logistic regression, random effects models, general estimating equations, robust variance estimates, and the random selection of one case from each outbreak. Age and mode of transmission were the only epidemiologically and statistically significant covariates in our final models using the above approaches. Weighing observations in a logistic regression model by the inverse of their outbreak size appeared to be a relatively robust and valid means for modelling these data. Some analytical techniques, designed to account for clustering, had difficulty converging or producing realistic measures of association.

The use of randomization tests to assess the degree of similarity in PFGE patterns of E. coli O157 isolates from known outbreaks and statistical space-time clusters.

Using isolates from reported cases of Escherichia coli O157 from Alberta, Canada in 2002, we applied randomization tests to determine if cases associated with an outbreak or statistical space-time cluster had more similar pulsed-field gel electrophoresis patterns, based on Dice coefficients, than expected by chance alone. Within each outbreak and space-time cluster, we assessed the mean, median, 25th percentile, 75th percentile, standard deviation, coefficient of variation, and interquartile range of the Dice coefficients of each pairwise comparison among the isolates. To assess the statistical significance of measures of location (e.g. mean) and variation (e.g. standard deviation) we created randomization distributions using all isolates or only isolates from sporadic cases. We determined that randomization tests are an appropriate tool for evaluating the similarity among isolates from cases that have been linked epidemiologically or statistically. We found little difference between using all cases or only sporadic cases when creating our randomization distributions.

The use of outbreak information in the interpretation of clustering of reported cases of Escherichia coli O157 in space and time in Alberta, Canada, 2000-2002.

We obtained a list of all reported cases of Escherichia coli O157 in Alberta during the 2000-2002 period, and using scan statistics we identified yearly temporal and spatial clusters of reported cases of E. coli O157 during the summer and in southern Alberta. However, the location of the spatial cluster in the south was variable among years. The impact of using both outbreak and sporadic data or only sporadic data on the identification of spatial and temporal clusters was small when analysing individual years, but the difference between spatial clusters was pronounced when scanning the entire study period. We also identified space-time clusters that incorporated known outbreaks, and clusters that were suggestive of undetected outbreaks that we attempted to validate with molecular data. Our results suggest that scan statistics, based on a space-time permutation model, may have a role in outbreak investigation and surveillance programmes by identifying previously undetected outbreaks.

Measles vaccination of infants in a well-vaccinated population.

During outbreaks of measles, measles vaccine is recommended for infants considered to be at risk who are 6 months of age and older. In a prospective trial the serologic response to early measles immunization has been evaluated in 125 infants given monovalent measles vaccine at 6 to 8.5 months of age and measles-mumps-rubella at 15 months. The response to vaccination was measured by plaque reduction neutralization (PRN) assay and enzyme immunoassay. Infants were grouped by the mother's immunization history: natural immunity (n = 60, Group 1); killed followed by live, further attenuated vaccine (n = 22, Group 2); and live, further attenuated vaccine only (n = 43, Group 3). The prevaccination geometric mean titer (GMT) by PRN for Group 1 (GMT = 69) was significantly higher than that of Group 2 (GMT = 18) or 3 (GMT = 13). Seroconversion (4-fold increase in PRN titer) rates after monovalent vaccine were 31, 71 and 76% for Groups 1, 2 and 3, respectively. Seroconversion percentages were higher when measured 6 to 8 weeks after vaccination compared with 4 to 5 weeks. After measles-mumps-rubella > or = 97% of all infants had PRN titers > 120 and were measles IgG-positive by enzyme immunoassay. These data show that as demographics shift to a well-vaccinated maternal population and susceptibility in younger infants, measles vaccination before the currently recommended age will be effective.

Reduced measles immunity in infants in a well-vaccinated population.

The recommended age for measles vaccination is based in part on information gathered when most mothers had natural measles. Nowadays many mothers have received measles vaccine. To assess this change measles antibody neutralization titers (NT) were determined for 278 mother-infant pairs. One hundred sixty-four mothers, born before 1958, likely had had natural measles (Group 1). Sixty mothers received one to three killed plus one attenuated measles vaccination (Group 2) and 54 received 1 attenuated measles vaccination only (Group 3). NT were determined for the mother and for the infant at birth and in the infant during the fourth and sixth months. Group 1 mothers and infants at every age had higher geometric mean NT than those in Groups 2 or 3 (P less than 0.05). By 7 months 65% of Group 1 infants and greater than 90% of Group 2 and 3 infants had an NT less than 1:10. The rate of antibody decay was significantly faster for Group 1 infants (P less than 0.05). Earlier vaccination in the infant should be considered.