Listeria monocytogenes

Etiology

Members of the genus Listeria are facultatively anaerobic, non–spore-forming, motile, gram-positive bacilli that are catalase positive. In the laboratory, Listeria can be distinguished from other gram-positive bacilli by their characteristic tumbling motility and growth at cold temperature (4-10°C [39.2-50°F]). The 6 Listeria spp. are divided into 2 genomically distinct groups on the basis of DNA-DNA hybridization studies. One group contains the species Listeria grayi, considered nonpathogenic. The 2nd group contains 5 species: the nonhemolytic species Listeria innocua and L. welshimeri and the hemolytic species Listeria monocytogenes, L. seeligeri, and L. ivanovii. Listeria ivanovii is pathogenic primarily in animals, and the vast majority of both human and animal disease is caused by L. monocytogenes.

Subtyping of L. monocytogenes isolates for epidemiologic purposes has been attempted with the use of heat-stable somatic O and heat-labile flagellar H antigens, phage typing, pulsed-field gel electrophoresis, ribotyping, and multilocus enzyme electrophoresis. Electrophoretic typing demonstrates the clonal structure of populations of L. monocytogenes as well as the sharing of populations between human and animal sources. Subtyping is an important component of determining whether cases are connected or sporadic but usually requires collaboration with a specialized laboratory.

Selected biochemical tests, together with the demonstration of tumbling motility , umbrella-type formation below the surface in semisolid medium, hemolysis, and a typical cyclic adenosine monophosphate test, are usually sufficient to establish a presumptive identification of L. monocytogenes.

Epidemiology

Listeria monocytogenes is widespread in nature, has been isolated throughout the environment, and is associated with epizootic disease and asymptomatic carriage in >42 species of wild and domestic animals and 22 avian species. Epizootic disease in large animals (e.g., sheep, cattle) is associated with abortion and “circling disease,” a form of basilar meningitis. L. monocytogenes is isolated from sewage, silage, and soil, where it survives for >295 days. Human-to-human transmission rarely occurs except in maternal-fetal transmission. The annual incidence of listeriosis decreased by 36% between 1996 and 2004 and has remained level since then. However , food-borne outbreaks continue to occur. In 2011, 84 cases and 15 deaths in 19 states were traced to cantaloupes from a single source. The cases were connected by use of pulsed-field gel electrophoresis, which showed that 4 different strains traced to the same source. The rate of Listeria infections varies among states. Epidemic human listeriosis has been associated with food-borne transmission in several large outbreaks, especially in association with aged soft cheeses; improperly pasteurized milk and milk products; contaminated raw and ready-to-eat beef, pork, and poultry, and packaged meats and salads; and vegetables both fresh and frozen harvested from farms where the ground is contaminated with the feces of colonized animals. Food-borne outbreaks in 2016 included raw milk, packaged salads, and frozen vegetables. The ability of L. monocytogene s to grow at temperatures as low as 4°C (39.2°F) increases the risk for transmission from aged soft cheeses and stored contaminated food. Listeriosis is an uncommon but important recognized etiology of neonatal sepsis and meningitis. Small clusters of nosocomial person-to-person transmission have occurred in hospital nurseries and obstetric suites. Sporadic endemic listeriosis is less well characterized. Likely routes include food-borne infection and zoonotic spread. Zoonotic transmission with cutaneous infections occurs in veterinarians and farmers who handle sick animals.

Reported cases of listeriosis are clustered at the extremes of age. Some studies show higher rates in males and a seasonal predominance in the late summer and fall in the Northern hemisphere. Outside the newborn period and during pregnancy, disease is usually reported in patients with underlying immunosuppression, with a 100-300 times increased risk in HIV-infected persons and in the elderly population ( Table 215.1 ). In a recent surveillance study from England, malignancies accounted for one third of cases, with special risk associated with cancer in elderly persons.

The incubation period, which is defined only for common-source food-borne disease, is 21-30 days but in some cases may be longer. Asymptomatic carriage and fecal excretion are reported in 1–5% of healthy persons and 5% of abattoir workers, but duration of excretion, when studied, is short (<1 mo.).

Pathology

One of the major concepts of Listeria pathology and pathogenesis is its ability to survive as an intracellular pathogen. Listeria incites a mononuclear response and elaboration of cytokines, producing multisystem disease, particularly pyogenic meningitis. Granulomatous reactions and microabscess formation develop in many organs, including liver, lungs, adrenals, kidneys, central nervous system (CNS), and notably the placenta. Animal models demonstrate translocation , the transfer of intraluminal organisms across intact intestinal mucosa. Histologic examination of tissues, including the placenta, shows granulomatous inflammation and microabscess formation. Intracellular organisms can often be demonstrated with special stains.

Pathogenesis

Listeria organisms usually enter the host through the gastrointestinal (GI) tract. Gastric acidity provides some protection, and drugs that raise gastric pH may promote infection. Studies of intracellular and intercellular spread of L. monocytogenes have revealed a complex pathogenesis. Four pathogenic steps are described: internalization by phagocytosis, escape from the phagocytic vacuole, nucleation of actin filaments, and cell-to-cell spread. Listeriolysin , a hemolysin and the best-characterized virulence factor, probably mediates lysis of vacuoles and is responsible for the zone of hemolysis around colonies on blood-containing solid media. In cell-to-cell spread, locomotion proceeds via cytochalasin-sensitive polymerization of actin filaments, which extrude the bacteria in pseudopods, which in turn are phagocytosed by adjacent cells, necessitating escape from a double-membrane vacuole. This mechanism protects intracellular bacteria from the humoral arm of immunity and is responsible for the well-known requirement of T-cell–mediated activation of monocytes by lymphokines for clearance of infection and establishment of immunity. It appears that secretion of cyclic di-adenosine monophosphate by the bacteria induces the host to produce interferon, which activates the immune system to fight the organism. The significant risk for listeriosis in patients with depressed T-cell immunity speaks for the role of this arm of the immune system. The role of opsonizing antibody in protecting against infection is unclear. In addition, siderophores scavenge iron from the host, enhancing growth of the organism and likely explaining the relatively high risk of listeriosis in iron overload syndromes.