Health Impact of Zoonotic Salmonella and Other Foodborne Bacterial Gastrointestinal Infections, with Particular reference to Antimicrobial Drug Resistance in Salmonella Typhimurium
PhD thesis, University of Copenhagen, 2005
By Morten Helms
Department of Epidemiology Research
Statens Serum Institut
Background
Foodborne bacterial gastrointestinal infections are important causes of morbidity and mortality worldwide and in spite of successful control programmes in some developed countries, these infections continue to have a major impact on the public health and economy of industrialised countries. A particular concern is the growing proportion of strains within zoonotic Salmonella serotypes which are becoming resistant to one or more antimicrobial drugs important to human medicine.
In the present thesis we use Danish population-based registries and patient questionnaires to study the impact on human health of zoonotic Salmonella and other foodborne bacterial pathogens in terms of hospitalisation, severe complications, long-term sequelae and death. Furthermore we estimate the risk of invasive illness or death associated with infection with antimicrobial drug-resistant Salmonella Typhimurium compared with pansusceptible strains of Salmonella Typhimurium.
Material and Methods
In four registry-based, matched cohort studies we linked data from the Danish Surveillance Registry for Enteric Pathogens with the Civil Registration System in order to create a reference group of ten persons for every patient and to obtain information on vital status for patients and referents. From the National Registry of Patients we obtained data on all hospital admissions and discharge diagnoses within the time span of up to ten years prior to entry in the study to one year after. This allowed us to control for pre-existing illness (comorbidity) and to determine the risk of hospitalisation associated with severe gastroenteritis, complications or long-term sequelae.
In a clinical cohort study we obtained detailed information on prevalence and duration of clinical symptoms associated with Salmonella Typhimurium infection, through patient questionnaires, questionnaires filled out by the patient’s primary health care provider and through examination of medical records.
Results
Morbidity: In 52,783 patients with non-typhoidal Salmonella, Campylobacter, Yersinia enterocolitica, E. coli and Shigella infection, 7,524 (14.4%) persons were hospitalised with a diagnosis of gastroenteritis within 90 days of infection. Large differences were observed depending on bacterial species: 17.7% of the patients with Salmonella infection compared with 10.8 % of patients with Campylobacter infection were hospitalised. Admission associated with complications within 90 days occurred for 647 (1.2%) patients. The risk of admission to hospital associated with invasive illness was more than six fold higher in patients with Salmonella infections (OR 30.3, 95% CI 26.2-35.1, compared with the background population) than in patients with Campylobacter-associated infections (OR 4.9, 95% CI 3.5-6.8)(p<0.001). hospitalisation associated with long-term sequelae was seen in 865 patients (1.7%). the risk of admission associated with reactive arthritis was more than twice as common in patients with salmonella (or 7.0, 95% ci 5.5-9.0) and yersinia enterocolitica (or 8.4, 95% ci 5.0-14.0) compared with campylobacter infection (or 3.1, 95% ci 2.0-4.8) (p<0.001 and p="0.002," respectively). in denmark, in 2003 there were 5,736 culture-confirmed cases of foodborne bacterial infection (including stec), contributing a total of 5,812 days of hospital stay.
Mortality: Among 48,857 people with Salmonella, Campylobacter, Yersinia enterocolitica and Shigella infections, 1,071 (2.2%) people died within one year after infection compared with 3,636 (0.7%) in the matched reference group. The relative mortality within one year was 3.1 times higher in patients than in referents. 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 (RR 2.53, 95% CI 1.38-4.62) and from six months to one year after infection with Campylobacter (1.35, 95% CI 1.02 to 1.80) and Salmonella (1.53, 95% CI 1.31 to 1.79). Among 5,609 cases with culture-confirmed cases associated with the four pathogens, a total of 61 deaths were attributable to the infection.
Impact of antimicrobial drug resistance: Prior antimicrobial drug treatment, within 30 days of Salmonella infections, was a risk factor among patients with multidrug-resistant Salmonella Typhimurium R-type ACSSuT compared with infection with pansusceptible Salmonella Typhimurium (OR 5.1, 95% CI 1.5-17.8). In a group of 2,047 patients with Salmonella Typhimurium, they were 2.3 times more likely to die within two years of infection than the general population upon adjusting for comorbidity. Patients with multidrug-resistant strains, resistant at least to R-type ACSSuT had a 4.8 times (95% CI 2.2-10.5) higher mortality within two years of infection upon adjusting for comorbidity compared with the matched sample from the general population. Finally, infection with a quinolone-resistant Salmonella Typhimurium was associated with a 3.2 (95% CI 1.4-7.1) times higher risk of invasive illness or death within 90 days of infection compared with the pan-susceptible strains.
Conclusions
Methods: The registry-based studies show that the Danish Surveillance Systems and population-based registries can be used to determine outcomes and estimate the burden of health of foodborne bacterial infections and likely other infectious diseases as well. Use of data from the National Registry of Patients and the Cancer Registry represents a feasible option when adjustment for severe, underlying illness is wanted.
Foodborne bacterial infections cause considerable morbidity in terms of hospital admission due to severe diarrhoea, complications and long-term sequelae. The current estimates on the burden of foodborne diseases in terms of mortality underestimate the impact of bacterial gastrointestinal infections. A particular risk is associated with antimicrobial drug resistance in Salmonella Typhimurium. Prior antimicrobial drug treatment is a risk factor for infection with multidrug-resistant Salmonella Typhimurium R-type ACSSuT. Quinolone resistance in Salmonella Typhimurium is associated with increased risk of invasive illness and excess mortality.
Sidst redigeret 29. juni 2010