Listeriosis

In 2015, there was a large outbreak of listeriosis gastroenteritis in 6 community settings (144 children and 10 staff) in Paderborn, Germany.

Bacteria of the genus Listeria (L.) are globally distributed, Gram-positive, motile, non-spore-forming, catalase-positive and facultatively anaerobic rods. They are characterized by motility at 200C but not at 370C. Listeria are widely distributed in the environment and can be found in soil, water, on plants. Listeria monocytogenes, the most important member of the genus Listeria in terms of uman medicine, secretes listeriolysin O, a pore-forming toxin. On culture media containing blood, this toxin causes β-haemolysis, which can be used to distinguish virulent from avirulent strains (however, this has no practical relevance -Hof H 2019).

The genus Listeria (sensu stricto) comprises 6(7) species, of which only L. monocytogenes, and to a very small extent L. seeligeri and L. ivanovii, are pathogenic to humans:

• L. monocytogenes: by far the most important human pathogenic species. L. monocytogenes can be subdivided into 13 serovars (serotypes), of which serovars 4b, 1/2a and 1/2b are associated with human disease.
• L. seeligeri: so far only detected in a few human diseases.
• L. ivanovii: so far only detected in a few human diseases.
• L. innocua: mostly apathogenic species
• L. welshimeri: apathogenic species
• L. murrayi (syn. L. grayi): apathogenic species
• L. rocourtiae: newly described species, so far no evidence of human pathogenicity.

Incidence: The annual incidence of cases of invasive listeriosis (A32.-) in the Federal Republic of Germany varies between 300 and 600 cases per year. Pregnancy-associated listeriosis affects 10% of all reported cases of listeriosis (both mother and newborn).

Route of infection: Listeriosis is in principle a food-borne infectious disease. Listeria can be found in a variety of animal foods (poultry, meat, meat products such as sausage, fish, fish products (especially smoked fish), milk and dairy products (especially cheese). Listeria are also frequently found on plant foods, e.g. on pre-cut salads. In addition to contamination of the source material, listeria can also be found in food processing plants. In the case of listeriosis of a pregnant woman or her child, the infection occurs during pregnancy (transplacental), during birth when passing through the birth canal, or postnatally through contact. For immunocompromised patients in hospitals, listeria is important as a pathogen of rare nosocomial infections.

The non-pregnancy-associated invasive listerioses mainly affect persons > 50 years of age and mainly immunosuppressed persons. Men > women. The disease is associated with CNS involvement (mainly meningitis) in 30% of infected persons and with sepsis in 30% of infected persons.

Incubation period: a few hours to six days for gastrointestinal symptoms; 1-12 days for septic course, 1-14 days for neuroinvasive manifestations. In pregnancy-associated cases, an incubation period of 17-67 days can be assumed.

Infection with Listeria usually only leads to local colonization of the intestinal tract. Infection rarely occurs in immunocompetent people. This often takes the form of mild, uncharacteristic, self-limiting, febrile gastroenteritis, including vomiting and diarrhea.

The risk of a manifest serious illness exists mainly for immunocompromised persons such as newborns, the elderly, patients with chronic illnesses or immunosuppressive therapy (e.g. tumor patients, transplant patients) and pregnant women. In very rare cases, sepsis may occur, which cannot be distinguished from sepsis of a different origin.

CNS involvement: Bacteremia may lead to purulent meningitis. Encephalitis with various neurological deficits (ataxia and/or impaired consciousness) is very rare. In principle, any organ can be affected in the course of listeriosis (arthritis, endocarditis or conjunctivitis, purulent dermatitis).

After contact with infected animals or contaminated soil, local papular or pustular skin lesions may occur (see listeriosis of the skin below)

In pregnant women, the disease usually progresses with a relatively inconspicuous flu-like picture or sometimes even without symptoms. There is a risk of intrauterine infection, first of the placenta and then of the unborn child. This can lead to premature birth or stillbirth (Craig AM et al. 2019).

In neonatal listeriosis:

• an early infection (connatal listeriosis: onset of symptoms in the 1st week of life)
• and
• a late infection (onset of symptoms from the 2nd week of life)

are distinguished. The early infection is characterized by sepsis, respiratory distress syndrome and skin lesions(granulomatosis infantiseptica). Infants with a late infection are usually born at term and pick up the pathogen as they pass through the birth canal. They often develop meningitis.

Duration of contagiousness: Infected persons can excrete the pathogen in their stool for several months. In mothers of infected newborns, the pathogens can be detected in lochial secretions and urine for about 7-10 days after delivery, rarely longer.

Laboratory diagnostics in human medicine: Pathogens can be detected from blood, cerebrospinal fluid, pus, vaginal secretions, lochia, stool, meconium or autopsy material. The type of cultural detection depends on the expected accompanying flora in the sample (direct cultural detection or cultivation of the pathogen after enrichment). The pathogens are undemanding and grow on the usual culture media. A weak haemolysis can usually be seen on blood agar. Although Listeria causes febrile gastroenteritis, it is also found in the stool of up to 5% of healthy individuals.

The cultured strains (on sheep blood agar morphology similar to group B streptococci, gram-positive possibly apparently gram-labile, partly coccoid rods) are distinguished from other Listeria species by the positive CAMP test and further biochemical investigations. MALDI-TOF mass spectrometers also allow species identification, which should be confirmed by conventional methods due to the magnitude of the diagnosis.

Detection of Listeria in clinical specimens is also possible by PCR and helpful if cultural detection is no longer successful (e.g. after antibiotic pretreatment). The molecular biological fine typing of Listeria is important for epidemiological questions and serves to clarify chains of infection and connections to suspect foods. Currently, the highest resolution of clonality of isolates is achieved by "whole genome sequencing (WGS)" and "core genome multi locus sequence typing (cgMLST)" or "SNP calling" (Note: all L. monocytogenes isolates should be sent to the Binational Consiliary Laboratory for Listeria in Vienna or to the Department 11 "Bacterial Infections" of the RKI, where the L. monocytogenes isolates are compared with a database in order to detect disease outbreaks at an early stage and to establish possible links to contaminated food).

The drug of first choice is amoxicillin or ampicillin high dose, combined with an aminoglycoside. Secondarily, cotrimoxazole is recommended.

Alternative drugs are controversially discussed (e.g. moxifloxacin, macrolides, linezolid).

Duration of therapy: at least 3 weeks, in case of CNS involvement 6 weeks, in case of endocarditis 4-6 weeks. Antibiotic resistance plays practically no role at present with ampicillin, gentamicin and cotrimoxazole, so that the therapeutic decision can be made safely before the antibiogram is available. Poor response to therapy is nevertheless not uncommon and is due to the intracellular lifestyle of the pathogen, immunosuppression in many patients and difficult, often late diagnosis. Despite targeted therapy, there is a relatively high lethality of manifest listeriosis (in recent years, about 21% of listeria septicaemias and 13% of listeria meningitis were fatal).

Preventive measures: Infection control and hygiene measures: Listeria monocytogenes are mainly found in unheated food from animals. Foodstuffs, especially vacuum-packed foodstuffs, should be consumed as soon as possible after purchase and well before the expiry of the stated minimum storage life. Vacuum packaging and refrigerator storage do not protect against the multiplication of Listeria, as is the case with other food-borne pathogens. On the contrary, long storage times can lead to a selective multiplication of Listeria.

Risk groups, especially pregnant women and patients with severe underlying diseases or immunosuppression, should refrain from eating the following foods: raw meat products (e.g. minced meat ) and raw sausage (e.g. salami), raw fish as well as smoked and marinated fish products, pre-cut packaged leaf sal ads (prepare leaf salads fresh yourself), soft raw milk cheese.

In recent years, there have been two major outbreaks of disease in Germany and Austria caused by sour milk cheese (Harzer Käse/Quargel) produced from pasteurised milk. The risk of infection associated with the consumption of soft and sour milk cheeses made from pasteurised milk cannot be conclusively assessed. However, it is also advisable for risk groups to refrain from consuming them as a precautionary measure.

Vaccination prophylaxis: Vaccination prophylaxis against listeriosis is not available. Measures in case of individual cases: Isolation of affected persons is not necessary. An exception may be women who have recently given birth to a child with listeriosis. In this case, nosocomial transmissions in obstetric wards have been described.

Measures to be taken in the eventof outbreaks: The competent public health authority must be informed of any listerioses that occur as part of the compulsory reporting system, so that outbreaks can be identified at an early stage and measures to contain them can be initiated.

In the event of suspected foodborne infections, it is essential to cooperate with the veterinary and food control authorities. Where possible, food should be preserved from refrigerators in patient households and examined by the relevant food inspection authority.

Legal basis (obligation to report according to IfSG): According to § 7 para. 1 IfSG, the public health department is notified by name of direct evidence of Listeria monocytogenes from blood, cerebrospinal fluid or other normally sterile substrates as well as from smears of newborns, insofar as it indicates an acute infection. The notifications must be received by the public health department no later than 24 hours after knowledge has been obtained.

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