Jacob Simonsen

Adverse Health Events Associated with Antimicrobial Drug Resistance in Campylobacter Species: A Registry-Based Cohort Study

BACKGROUND Resistance to clinically important antimicrobial agents, particularly fluoroquinolones and macrolides, is increasing among Campylobacter isolates, but few studies have explored the human health consequences of such resistance. METHODS In a registry-based cohort study, we determined the risk of invasive illness and death associated with infection with quinolone- and erythromycin-resistant Campylobacter strains, while adjusting for comorbidity. We linked data from the Danish Surveillance Registry for Enteric Pathogens with data from the Civil Registration System and National Health Registries. RESULTS Of 3471 patients with Campylobacter infection, 22 (0.63%) had an adverse event, defined as invasive illness or death, within 90 days of the date of receipt of samples. Patients infected with quinolone-resistant Campylobacter strains had a 6-fold increased risk of an adverse event within 30 days of the date of receipt of samples, compared with patients infected with quinolone- and erythromycin-susceptible Campylobacter strains (adjusted odds ratio [AOR], 6.17 [95% confidence interval {CI}, 1.62-23.47]). However, infection with erythromycin-resistant strains was associated with a >5-fold risk of an adverse event within 90 days of the date of receipt of samples (AOR, 5.51 [95% CI, 1.19-25.50]). CONCLUSIONS The present study provides evidence of the human health consequences of resistance to clinically important agents among Campylobacter infections and the need for increased efforts to mitigate such resistance.

Quinolone Resistance Is Associated with Increased Risk of Invasive Illness or Death during Infection with Salmonella Serotype Typhimurium

In a registry-based cohort study, we determined the risk of invasive illness or death associated with infection with quinolone-resistant Salmonella serotype Typhimurium. We linked data from the Danish surveillance registry of enteric pathogens with data from the Danish civil registration system and 2 national health registries. Of 1323 patients infected with Salmonella Typhimurium, 46 (3.5%) were hospitalized due an invasive illness within 90 days of infection, and 16 (1.2%) died within 90 days of infection. After adjustment for age, sex, and comorbidity, infection with quinolone-resistant Salmonella Typhimurium was associated with a 3.15-fold (95% confidence interval, 1.39-7.10-fold) higher risk of invasive illness or death within 90 days of infection, compared with that observed for infection with pansusceptible strains.

The causal direction in the association between respiratory syncytial virus hospitalization and asthma.

BACKGROUND Earlier studies have reported an increased risk of asthma after respiratory syncytial virus (RSV) hospitalization. Other studies found that asthmatic disposition and propensity to wheeze increase the risk of RSV hospitalization. OBJECTIVE The current study examined the causal direction of the associations between RSV hospitalization and asthma in a population-based cohort of twins. METHODS We conducted a prospective cohort study examining the associations between RSV hospitalization and asthma by using registry information on RSV hospitalization and asthma among 18,614 Danish twins born 1994 to 2003. The associations between RSV and asthma were examined in both directions: we examined the risk of asthma after RSV hospitalization, and the risk of RSV hospitalization in children with asthma in the same population-based cohort. RESULTS Asthma hospitalization after RSV hospitalization was increased as much as 6-fold to 8-fold during the first 2 months after RSV hospitalization but was no longer increased 1 year later. Asthma increased the risk of RSV hospitalization by 3-fold, and the risk was not time-dependent. Analyzing these associations on the basis of asthma defined from use of inhaled corticosteroid did not materially change the risk estimates. CONCLUSION There is a bidirectional association between severe RSV infection and asthma. Severe RSV infection is associated with a short-term increase in the risk of subsequent asthma, suggesting that RSV induce bronchial hyperresponsiveness; and asthma is associated with a long-term increased susceptibility for severe RSV disease, suggesting a host factor being responsible for the severe response to RSV infection. This suggests that severe RSV infection and asthma may share a common genetic predisposition and/or environmental exposure.

Foodborne Bacterial Infection and Hospitalization: A Registry-Based Study

Background. Foodborne bacterial gastrointestinal infections are important causes of morbidity and mortality worldwide, and despite successful control programs in some developed countries, these infections continue to have a major impact on public health and economy. Methods. On the basis of data from 3 national registries, we determined short- and long-term risks of hospitalization due to gastroenteritis, short-term complications, and long-term sequelae after infections with nontyphoid Salmonella enterica, Campylobacter species, Yersinia enterocolitica, diarrheagenic Escherichia coli, and Shigella species. Results. Among 52,121 patients, 7524 (14.4%) were hospitalized with a diagnosis of gastroenteritis within 90 days after microbiological diagnosis. A total of 4941 patients (17.7%) with infections due to S. enterica and 1937 (10.8%) with infections due to Campylobacter species were admitted to the hospital. Complications, such as gastrointestinal perforation and invasive illness, occurred in 647 patients (1.2%). The risk of invasive illness was >6-fold higher in patients with infections due to S. enterica (odds ratio [OR] compared with the general population, 30.3; 95% confidence interval [CI], 26.2-35.1) than in those with infections due to Campylobacter species (OR, 4.9; 95% CI, 3.5-6.8) (P<.001). Long-term sequelae were seen in 865 patients (1.7%). Among 1000 patients with infections due to S. enterica, 1820 days of hospital stay were attributable to gastroenteritis, complications, and long-term sequelae. The corresponding figure for Campylobacter infections was 714 days. Conclusions. Infections with bacteria that are usually foodborne cause considerable morbidity, in terms of severe gastroenteritis that requires admission to hospital, as well as complications and long-term sequelae. The risk of complications and sequelae depends on bacterial species, and nontyphoid Salmonella is particularly associated with a burden of severe morbidity.

Trends in Overall and Cause-Specific Mortality Among Patients With Inflammatory Bowel Disease From 1982 to 2010

BACKGROUND & AIMS Treatments for inflammatory bowel diseases (IBDs) such as ulcerative colitis (UC) and Crohns disease (CD) have changed over time, with unclear effects on prognosis. We assessed overall and cause-specific mortality in a Danish cohort of patients with IBD during a 30-year time period. METHODS We compared data from 36,080 patients with UC and 15,361 with CD, who were diagnosed in Denmark from 1982 to 2010, and compared them with data from 2,858,096 matched individuals from the general population (controls). Overall and cause-specific mortality were estimated by Cox regression analysis, adjusted for age, sex, disease duration, and known comorbidities before IBD diagnosis. Results were presented as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS Mortality greatly increased in the first year after individuals were diagnosed with IBD; intermediate-term and long-term mortalities increased by approximately 10% among individuals with UC and 50% among those with CD, compared with the general population. Compared with the time period of 1982-1989, overall mortalities decreased among patients diagnosed with UC from 1990 to 1999 (HR, 0.96; 95% CI, 0.90-1.02) and from 2000 to 2010 (HR, 0.88; 95% CI, 0.82-0.95). These reductions were mainly due to decreased mortality from colorectal cancer, gastrointestinal disorders, and suicide. For individuals with CD, mortality did not change among these time periods because of long-term increases in mortality from infections, cancer, respiratory diseases, and gastrointestinal diseases. CONCLUSIONS In a Danish cohort, mortality from UC decreased from 1982 to 2010, largely because of reduced mortalities from gastrointestinal disorders and colorectal cancer. People with CD had 50% greater mortality than the general population, and this value did not change during this time period.

Enteric Salmonella or Campylobacter infections and the risk of inflammatory bowel disease

Objective Enteric pathogens have been implicated in the aetiology of inflammatory bowel disease (IBD), but increased rates of stool testing of patients with unclear gastrointestinal symptoms might cause detection bias. Hence, the objective of this study was to analyse incidence rates of Crohns disease and ulcerative colitis among patients with Salmonella- or Campylobacter-positive and negative stool tests and to study the incidence of positive and negative stool tests among patients already diagnosed with IBD. Methods The Danish population was followed for 94.3 million person-years during 1992–2008 using national registers to identify persons with positive and negative stool tests and patients with IBD. Using Poisson regression, incidence rate ratios (IRRs) for IBD after positive or negative stool tests and, conversely, IRRs for positive and negative stool tests following IBD, were calculated. Results IRRs for IBD were significantly high in the first year after Salmonella- or Campylobacter-positive stool tests (IRRs 5.4–9.8), and they remained moderately increased 1–10 years later (IRRs 1.6–2.2), and less so >10 years later (IRRs 0.8–1.8). However, IRRs for IBD <1 year after a negative stool test were several-fold higher (IRRs 53.2–57.5), and a decreasing incidence pattern over time was parallel to that following positive test results. Among patients with IBD, IRRs for subsequent positive and—most notably—negative stool test results were also significantly high. Conclusion Similarities in temporal risk patterns for IBD following positive or negative stool tests indicate that the increased occurrence of Salmonella- or Campylobacter-positive results around the time of first IBD hospitalisation results from detection bias.

Cesarean section and offspring's risk of inflammatory bowel disease: a national cohort study.

Background: Intestinal bacteria have been implicated in the etiology of the common inflammatory bowel diseases (IBD) ulcerative colitis and Crohns disease. Because delivery by cesarean section disturbs the normal bacterial colonization of the newborns intestine, we determined the risk of IBD according to mode of delivery. Methods: A register‐based national cohort study of 2.1 million Danes born 1973–2008. The effect of mode of delivery on IBD incidence in the age‐span 0–35 years was estimated by means of confounder‐adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CIs) obtained in Poisson regression analysis. Information on mode of delivery was obtained from the Danish Medical Birth Registry and cases of IBD were identified in the Danish National Patient Registry 1977–2008. Results: During 32.6 million person‐years of follow‐up, a total of 8142 persons were diagnosed with IBD before age 36 years. Cesarean section was associated with moderately, yet significantly, increased risk of IBD at age 0–14 years (IRR 1.29, 95% CI 1.11–1.49), regardless of parental disposition to IBD. Assuming causality, an estimated 3.2% of IBD cases before age 15 years were attributable to cesarean section. Conclusions: Rates of IBD with onset in childhood are moderately increased after birth by cesarean section but underlying mechanisms remain unclear. Even if the association is causal, the possible impact of increasing cesarean section practices on the overall burden of IBD in childhood is small. (Inflamm Bowel Dis 2011;)

Population-based study of the impact of childcare attendance on hospitalizations for acute respiratory infections.

OBJECTIVES. It is well known that children attending childcare have a higher risk of acute respiratory infections compared with children in home care; however, knowledge is sparse regarding how the excess risk of acute respiratory infection varies with age, time since enrollment, and other factors. METHODS. A national register-based study of 138821 inpatient admissions to hospital for acute respiratory infection during 3982925 person-years of follow-up in Danish children aged 0 to 5 years. Data on child and family characteristics, childcare attendance, and hospitalizations were obtained from Danish registries. The outcome of the study was inpatient admissions to hospital for acute respiratory infection. Incidence rate ratios were estimated using Poisson regression. RESULTS. In children <1 year of age, the first 6 months of enrollment in the first childcare facility were associated with a 69% higher incidence of hospitalizations for acute respiratory infection compared with children in home care. Similar figures for children aged 1, 2, and ≥3 years were 47%, 41%, and 8%, respectively. The incidence decreased after the first 6 months, and after ≥1 year in childcare the incidence was comparable with that of children in home care. Similar patterns were seen after second enrollment. For 0- to 2-year-old children living in households with no additional children <5 years, the excess incidence during the first 6 months of enrollment was 100% compared with 25% and 9% for children living with 1 and ≥2 additional children, respectively. CONCLUSIONS. The increased risk of acute respiratory infection was most pronounced among 0- to 2-year-old children living with no other children during the first 6 months of enrollment. Our findings may suggest that it would be optimal to postpone enrollment into childcare until after 1 year of age.

Socioeconomic risk factors for bacterial gastrointestinal infections.

Background: Bacterial gastrointestinal infections cause considerable morbidity in industrialized countries, but little is known about socioeconomic factors affecting the risk of infection. Methods: By linkage among 3 national registers, we followed the entire population of Denmark (5.3 million people) from 1993 to 2004 for the occurrence of laboratory-confirmed bacterial gastrointestinal infections. Using Poisson regression analyses, incidence rate ratios (IRRs) were estimated for the major groups of bacteria in different socioeconomic strata, focusing on income group, level of education, marital status, number of children in the household, and country of birth. Results: Associations with socioeconomic variables varied by type of bacterium. High-income groups had increased risks of infection with Campylobacter, Shigella, and Salmonella Enteritidis, and education was positively associated with increased risk of infection with Campylobacter and Shigella. Married persons were generally at higher risk than single persons, but adults with children had lower risks compared with adults without children. Foreign-born persons generally had lower risks, whereas Danish-born persons with foreign-born parents were at reduced risk of infection with the pork-associated bacterium Yersinia (IRR = 0.33; 95% confidence interval 0.25–0.42), but increased risk with Shigella (5.7; 4.8–6.1), Salmonella, and Shiga toxin-producing Escherichia coli. Conclusions: The findings suggest that risk of infection is not primarily associated with poverty, but rather with increasing socioeconomic status. Risk of infection also varies with cultural background. Observed differences may be explained by differences in diet and travel activity, although they may also in part reflect differential probabilities of diagnostic reporting.

Marriage, cohabitation and mortality in Denmark: national cohort study of 6.5 million persons followed for up to three decades (1982–2011)

BACKGROUND Living arrangements have changed markedly in recent decades, so we wanted to provide an up-to-date assessment of mortality as a function of marital status and cohabitation status in a complete population. METHODS We studied mortality in a national cohort of 6.5 million Danes followed for 122.5 million person-years during 1982-2011, using continuously updated individual-level information on living arrangements, socio-demographic covariates and causes of deaths. Hazard ratios (HRs) estimated relative mortality in categories of marital status, cohabitation status and combinations thereof. RESULTS HRs for overall mortality changed markedly over time, most notably for persons in same-sex marriage. In 2000-2011, opposite-sex married persons (reference, HR = 1) had consistently lower mortality than persons in other marital status categories in women (HRs 1.37-1.89) and men (HRs 1.37-1.66). Mortality was particularly high for same-sex married women (HR = 1.89), notably from suicide (HR = 6.40) and cancer (HR = 1.62), whereas rates for same-sex married men (HR = 1.38) were equal to or lower than those for unmarried, divorced and widowed men. Prior marriages (whether opposite-sex or same-sex) were associated with increased mortality in both women and men (HR = 1.16-1.45 per additional prior marriage). CONCLUSION Our study provides a detailed account of living arrangements and their associations with mortality over three decades, thus yielding accurate and statistically powerful analyses of public health relevance to countries with marriage and cohabitation patterns comparable to Denmarks. Of note, mortality among same-sex married men has declined markedly since the mid-1990s and is now at or below that of unmarried, divorced and widowed men, whereas same-sex married women emerge as the group of women with highest and, in recent years, even further increasing mortality.