Short and long term mortality associated with foodborne bacterial gastrointestinal infections: registry based studyCommentary: matched cohorts can be useful -- Helms et al. 326 (7385): 357 -- bmj.com

Objectives: To determine the excess mortality associated with infections with Salmonella, Campylobacter, Yersinia enterocolitica, and Shigella and to examine the effect of pre-existing illness. Design: Registry based, matched cohort study. Setting: Denmark. Participants: 48 857 people with gastrointestinal infections plus 487 138 controls from the general population. Main outcome measure: One year mortality among patients with gastrointestinal infections compared with controls after adjustment for comorbidity. Results: 1071 (2.2%) people with gastrointestinal infections died within one year after infection compared with 3636 (0.7%) controls. The relative mortality within one year was 3.1 times higher in patients than in controls. The relative mortality within 30 days of infection was high in all four bacterial groups. Furthermore, there was excess mortality one to six months after infection with Yersinia enterocolitica (relative risk 2.53, 95% confidence interval 1.38 to 4.62) and from six months to one year after infection with Campylobacter (1.35, 1.02 to 1.80) and Salmonella (1.53, 1.31 to 1.79). Conclusions: Infections with all these bacteria were associated with an increased short term risk of death, even after pre-existing illnesses were taken into account. Salmonella, Campylobacter, and Yersinia enterocolitica infections were also associated with increased long term mortality. What is already known on this topic Foodborne bacterial infections have a major effect on the public health and economy of industrialised countries Most estimates of mortality are short term and do not take into account coexisting illnesses What this study adds Patients infected with Salmonella, Campylobacter, Yersinia, and Shigella had higher 30 day mortality than controls after comorbidity was taken into account Salmonella, Campylobacter, and Yersinia infections were also associated with increased long term mortality The number of deaths from foodborne diseases is likely to be underestimated Introduction Foodborne bacterial infections have a major and perhaps increasing effect on the public health and economy of industrialised countries. – It is difficult to determine the exact mortality associated with bacterial infections that are usually foodborne. Pathogen specific surveillance systems rarely collect systematic information on outcomes of illness, and outcome specific surveillance systems (such as death certificates) greatly under-report many pathogen specific conditions. The quantification of the public health impact of bacterial foodborne infections is further complicated by their interaction with chronic underlying diseases and associated conditions. We report new estimates of the excess mortality associated with infections with Salmonella, Campylobacter, Yersinia enterocolitica, and Shigella spp. By using data from Danish population based registries, we determined the long term effect on survival adjusted for coexisting illness. Methods We obtained data for the study from the national registry of enteric pathogens, the Danish civil registration system, the national registry of patients, and the cancer registry. Bacterial foodborne infections are diagnosed at our institute and 10 local clinical microbiology laboratories. The institute is notified of positive findings and records them in the national registry of enteric pathogens. If a bacterial species or Salmonella serotype is found more than once from the same person within six months, only the first positive sample is registered. We included all patients with culture confirmed infections with non-typhoidal Salmonella, Campylobacter spp, Yersinia enterocolitica, or Shigella spp registered between 1 January 1991 and 31 October 1999. To compare the mortality of patients with that of people without known bacterial gastrointestinal infections, we used data from the civil registration system, which assigns a personal identification number to all liveborn children and citizens of Denmark. For every patient, we randomly selected 10 people matched for age, sex, and county of residence who were alive on the date the sample was received. We obtained information on vital status, date of death or emigration, and county of residence for patients and controls. Finally, we obtained data on all hospital discharges, outpatient attendances (since January 1995), and cancer diagnoses up to five years before entry in the study from the national registry of patients and the cancer registry. This allowed us to control for pre-existing illness (comorbidity). Statistical methods We created a comorbidity index using the principles described by Charlson et al. This index is a sum of weights corresponding to the number and severity of coexisting illnesses. We first calculated the relative mortality associated with different diagnostic groups, using data from the background population. These relative rates served as weights in the further survival analyses. We then created the index by adding log transformed weights, taking into account multiple discharges before entry into the study. We excluded diagnostic groups associated with a relative mortality less than 1.2. We forced this index into the survival analyses, so that any difference between the mortality of patients and the general population quantified mortality beyond that attributable to underlying illness. – To compare the mortality of patients with that of the general population, we stratified the data so that each stratum contained one patient and 10 controls. We preserved the matching in all analyses by using conditional proportional hazard regression to control for age, sex, and county of residence. The analysis was conducted with SAS software (version 6.12), with proportional hazards regression procedure (PHREG). Results During the study, 49 149 patients had bacterial gastrointestinal infections registered, 48 857 (99.4%) of whom could be linked to the civil registry system. Of these patients, 26 974 (55.2%) had Salmonella infection, 16 180 (33.1%) Campylobacter infection, 4045 (8.3%) Yersinia infection, and 1658 (3.4%) Shigella infection. A total of 1071 (2.2%) deaths were registered up to one year after infection compared with 3636 (0.7%) deaths among the 487 138 controls. Patients infected with one of the four enteric pathogens had a 3.1 times higher mortality than controls (95% confidence interval 2.89 to 3.33). A total of 2645 patients had one or more of the diseases included in the comorbidity index. Table 1 shows the number of patients and the various diagnostic groups used in the index, the weights of the diagnostic groups, and the relative risk of belonging to one of the diagnostic groups compared with the reference group. Underlying conditions were more common among patients than in the control group, particularly AIDS related illness, metastatic cancers, and lymphomas or leukaemia. After we adjusted for comorbidity, the relative mortality fell from 3.10 to 2.56 (95 % confidence interval 2.38 to 2.76). View this table: In this window In a new window Table 1 Comorbidity in 48 857 patients with Salmonella, Campylobacter, Shigella, and Yersinia infections, Denmark, 1991-9 Table 2 summarises the cumulative mortality (Kaplan-Meier estimates) and relative mortality by time since infection. The relative mortality in the 30 days after the episode date ranged from 3.63 to 22.03 for the four bacteria. No excess mortality was seen after 30 days for Shigella and 180 days for Yersinia enterocolitica, but for Salmonella and Campylobacter, we found an excess mortality up to one year after infection. View this table: In this window In a new window Table 2 Mortality among 48 857 patients with Salmonella, Campylobacter, Shigella, and Yersinia infection compared with matched controls from the general population and adjusted for comorbidity, Denmark, 1991-9 Table 3 shows the relative mortality before and after we adjusted for coexisting illness. After adjusting for comorbidity, we found that mortality in patients infected with Salmonella dublin was more than 12 times higher than in the control group. For other Salmonella serotypes, Campylobacter, and Yersinia enterocolitica mortality was 1.86 to 2.88 times higher than in the control group. Infection with Shigella species was not associated with higher mortality after we adjusted for comorbidity. 1 4