Invasive listeriosis is a rare but serious food-borne infection with the bacterium Listeria monocytogenes, which primarily affects immunocompromised persons due to disease, age or pregnancy. The incubation period is longer than that for most other food-borne infections, typically 2-3 weeks, but the period may vary from 1 to 70 days and L. monocytogenes may persist in, e.g., a food production environment for longer periods of time, thereby giving rise to prolonged disease outbreaks. Due to its severity and outbreak potential, Statens Serum Institut (SSI) has performed whole-genome sequencing on all isolates from invasive infections since 2014; and, if possible, all patients are interviewed to map exposures in the month before they presented with symptoms.
Listeriosis trends 2019-2022
During the period 2019-2022, a total of 252 cases of invasive infection (Figure 1) were registered. Of these infections, 16% were detected in spinal fluids and/or notified as purulent meningitis.
Annually, an average 63 cases were registered [range 43-86], which corresponds to an incidence of 1.08 per 100,000 inhabitants in Denmark per year.
Distribution by age, sex and area
Figure 2 presents the number of listeriosis cases in 2019-2022 by sex and age groups. Infections in pregnant women and/or their unborn/newly born children are registered as a single infection and recorded as a case in the mother. A total of 75% of the listeriosis cases were more than 65 years old, and 57% were female. During the period 2019-2022, listeria cases were observed in all Danish provinces, and the mean annual incidence ranged from 0.62 to 1.89 cases per 100,000 inhabitants.
Manifestation and mortality
During the period, a total of 41 (16%) cases presented with meningitis, an additional 80% of the infections were identified by blood culture (202 cases), and 4% of the infections were identified in other sampling material, e.g., the placenta. A total of 11 listeriosis cases were registered among pregnant women (1-4 annually). Among the cases registered in pregnant women, some cases led to abortion, still birth or the neonate died shortly after birth.
Among the 252 persons with listeriosis in the 2019-2022 period, 61 (24%) died within 30 days, which is consistent with previous reports.
Information was available about underlying predisposing diseases (e.g, cancer, blood disorders, renal disorders and diabetes), immunosuppressant therapy or pregnancy for 209 listeria cases, of which most (30%) had cancer and/or heart disease (16%).
Outbreaks and genetically related bacteria
All L. monocytogenes isolates are whole-genome sequenced. This allows for identification of clusters of genetically related bacteria (same type) and thus for identification and investigation of potential outbreaks. The multi-locus sequence type (MLST) is established for all isolates and named according to the internationally established nomenclature. Subsequently, the shared part of the genetic material can be analysed by core-genome-MLST (cgMLST, Moura et al. 2016). When comparing the sequences (using single linkage analysis), it is possible to establish the number of allele differences between the sequences. Genetically related listeria bacteria are defined as those that have ≤ 7 different alleles.
During the period 2019-2022, a total of 63% of the listeria cases were of a listeria type that was seen in a minimum of one other patient in the 2014-2022 period, and thus formed part of a genetic cluster.
In 2022, a significantly higher number of listeria cases (86) were observed compared to the usual, but the level was on a par with 2014 when a large outbreak occurred. Around 1/3 of the listeria cases recorded in 2022 were due to one of three different outbreaks. The number of sporadic cases (cases in which the listeria type has not previously been identified) was in line with what was registered in previous years (Figure 1).
During the period 2019-2022, a total of 12 larger genetic clusters/outbreaks counting eight or more cases was observed, these accounted for a total of 34% of all patients. Seven of the outbreaks that accumulated cases in the 2019-2022 period started before 2019 and five outbreaks started in 2019 or later.
The causes of three of the larger outbreaks were identified:
Spiced sliced meat rolls: In the spring of 2022, an outbreak caused by spiced sliced meat rolls was observed. A total of eight persons were identified with infection with the same type of listeria bacteria, sequence type 8. Patient interviews revealed that all had ingested spiced sliced meat roll in the month before presenting with symptoms and several of the patients shopped in the same chain of shops. During the traceback process, the Danish Veterinary and Food Administration identified several producers in Denmark and abroad. Sampling at Danish production facilities failed to identify listeria of the type causing the outbreak. The company abroad found Listeria monocytogenes in an own control samples from its production facility and shared the isolate with the Danish Veterinary and Food Administration. Whole-genome sequencing revealed that the listeria bacterium was similar to that of the outbreak type, and 16 spiced sliced meat roll products were recalled from the market.
Fish cakes: During the autumn of 2022, an outbreak caused by fish cakes produced in Denmark was observed. Here, a total of 11 persons were identified with the same type of listeria: sequence type 7. Interviews with the first four cases and information from shopping receipts showed that the patients had eaten or bought smoked fish products as well as fish cakes. The sampling of the smoked fish products performed by the Danish Veterinary and Food Administration did not identify L. monocytogenes, but the outbreak type was identified at the manufacturer of fish cakes, and the fish cakes were therefore recalled from the market.
Smoked fish products: In 2019, two Danish listeria cases that formed part of a prolonged outbreak with sequence type 1247 caused by smoked fish products in Estonia were identified. This outbreak comprised cases from a total of four European countries.
Other products: In 2019, three additional cases belonging to an outbreak with sequence type 1, which started in 2016, was observed. All of the patients resided in East Jutland when they presented with symptoms. In September 2019, interview data allowed investigators to conclude that several of the patients had shopped at the same greengrocers and had ingested hummus produced by the greengrocers. During a subsequent control visit to the company, the Danish Veterinary and Food Administration detected listeria in the food and production environment. The sequences from the listeria isolates of the patients and from the food and production environments were identical. The company discontinued production in accordance with an injunction issued by the Danish Veterinary and Food Administration, and consumers were recommended to discard hummus, olives provided in oil, dates, and other foods characterised by a high water activity bought at the greengrocers in question. Prolonged local listeria outbreak in Denmark, 2016-2019 (ssi.dk)
Unknown: The sources of the remaining nine outbreaks, each counting 8-14 disease cases, remain unknown. Three of these outbreaks are described at the SSI website:
Outbreak investigation and collaboration with the Danish Veterinary and Food Authority and DTU Food
Information from whole-genome sequencing and interviews are continually used to identify or verify potential sources of outbreaks, and sequences of isolates from patients and food or production environments are regularly being compared. Investigations of listeria outbreaks are conducted in collaboration with the Danish Veterinary and Food Administration and DTU Food under the auspices of the Central Outbreak Group. For more information about listeria, please see the Annual Report on Zoonoses 2022.