Risk Factors for Sporadic Non-Pregnancy Associated Listeriosis in Germany-Immunocompromised Patients and Frequently Consumed Ready-To-Eat Products

Abstract

Non-pregnancy associated (N-PA) listeriosis, caused by Listeria monocytogenes, is a rare but severe disease, and is predominantly food-borne. Most cases appear sporadic and their infection vehicle remains unknown. Incidence has increased since 2008 in Germany. We aimed to identify underlying conditions and foods associated with sporadic N-PA listeriosis in Germany. We performed a nationwide case-control study from March 2012-December 2013. Cases were sporadic N-PA listeriosis patients notified to public health. Control subjects were age (40-65 years, 66-75 years, ≥ 76 years) frequency-matched persons from a nationwide random telephone sample. A structured questionnaire collected information on underlying diseases, therapies and >60 food items. We conducted multivariable logistic regression analysis, adjusting for host factors identified by causal diagram theory, and calculated population attributable fractions. We enrolled 109 cases and 1982 controls. Cases' median age was 69 years, 55% were male, 44% received immunosuppressive therapy within 3 months prior to illness onset; a further 28% had at least one immunocompromising disease. In multivariable analysis, immunosuppressive therapy (OR 8.8, 95%CI 4.9-15.6), immunocompromising disease (OR 2.7; 95%CI 1.4-5.2), gastric acid suppression (OR 3.0; 95%CI 1.4-6.3), the consumption of cold cooked sausages (OR 2.6; 95%CI 1.6-4.4), the preferred consumption of packaged cheese (OR 2.1; 95%CI 1.3-3.5) and pre-sliced cheese (OR 2.2; 95%CI 1.3-3.7) were significantly associated with N-PA listeriosis. These foods accounted for 59% of all cases. Typical high risk foods, e.g. cold seafood, certain types of cheeses, tended to be negatively associated with disease. In conclusion, immunosuppressive therapy and frequently consumed ready-to-eat foods are the main risk factors for sporadic N-PA listeriosis in Germany. To reduce their risk, immunocompromised persons should consume the identified foods well before the 'use-by' date. The microbiological criteria for Listeria monocytogenes in ready-to-eat foods may insufficiently protect persons who are markedly immunocompromised.

Fig 1. Hypothesized causal structure of exposure, host factors and non-pregnancy associated listeriosis, Germany, 2012–2013 [–61].

* Proxy for socio-economic status Presumed causal relationships based on: Significant associations in scientific studies 1 Age-related changes of the immune system (immunosenescence) lead to increased susceptibility to infections [48] in general; risk for listeriosis increases with age [49] 2 Prevalence of chronic health conditions in Germany increases with age [50] 3 Dietary behavior of German adults depends on age [51, 52] 5 Socioeconomic status depends on age in a highly representative sample of the German population [13] 8 Presence of an underlying immunocompromising disease or therapy increases risk for listeriosis [24, 25] 9 Experimental evidence suggests increased susceptibility for listeriosis in male animals [53] 10 Socioeconomic status depends on sex in a highly representative sample of the German population [13] 11 Dietary patterns among German adults differ between the sexes [51] 13 Socioeconomic status influences nutrition pattern [54] 14 Health (morbidity) is related to socioeconomic status in highly representative samples of the German population [55] 18 Morbidity is related to sex in highly representative samples of the German population [50] 19 Prescription of gastric acid suppressors is related to sex in Germany [56] 21 Prescription of gastric acid suppressors is related to age in Germany [56] 23 Prevalence of reflux symptoms (indication for gastric acid suppression) is significantly associated to socioeconomic status in a highly representative sample of the German population [57]; chronic use of gastric acid suppressors is associated with low income and low educational level [58] 24 Gastric acid suppression lowered infectious dose of L. monocytogenes in animals [59] and was associated with listeriosis outbreak [60] Official Statistics: 17 Residence determines access to retailers, food handlers, farmer's markets etc. (www.lbv.brandenburg.de/dateien/stadt_wohnen/rb_Einzelhandel_Brandenburg_2011.pdf; last accessed on 18.12.2014) Assumptions: 4 Knowledge about listeriosis depends on age (e.g. by lifelong learning, age-dependent access to electronic media) 6 People with underlying disease are better informed about listeriosis through physicians or self-study 7 Consumption pattern of people with underlying immunocompromising diseases or therapy differ from those of healthy people (food intolerances, special diets etc.) 12 People with higher SES (educational background) are better informed about listeriosis 15 SES influences choice of residence 16 Susceptible persons who know listeriosis tend to avoid consumption of risk foods 20 Consumption pattern of people with gastric acid suppression differ from those of people without (weight loss diet is recommended as non-drug treatment for reflux diseases in German treatment guidelines) 22 High level of (inappropriate) prescriptions of gastric acid suppressors for hospitalized patients are continued in primary care [61]

Fig 2. Enrollment of non-pregnancy associated listeriosis cases.