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Listeriosis is a serious disease for humans, with a mortality greater than 25 percent. There are two main clinical manifestations, sepsis and meningitis (Fig. 16-1
). Meningitis is often complicated by encephalitis, which is exceptional among bacterial infections. Occasionally, pyogenic infections of various organs have been found. Relapses may occur after apparent recovery.
All Listeria species are small, Gram-positive rods, which are sometimes arranged in short chains. In direct smears they may be coccoid, so they can be mistaken for streptococci. Longer cells can be suggestive of corynebacteria. Flagella are produced at room temperature rather than at 37° C. Hemolysin production is an important marker for L monocytogenes, although it is not definitive, as L ivanovii and L seeligeri are likewise hemolytic on blood agar. Further biochemical characterization is necessary to distinguish between the different Listeria species.
It may be desirable for epidemiologic purposes to identify a particular strain by serotyping to characterize surface antigens, such as O antigens (teichoic acids) and H antigens (proteins). The serovars 1/2a and 4b are responsible for up to 90 percent of all cases of listeriosis.
A particular property of L monocytogenes is the ability to multiply at low temperatures (Fig. 16-2
). Bacteria therefore can accumulate in contaminated food stored in the refrigerator.
Listeria monocytogenes is presumably ingested with raw, contaminated food (Fig. 16-2
). An invasion factor secreted by the pathogenic bacteria enables them to penetrate host cells of the epithelial lining. Since this microorganism is widely distributed, this event may occur rather often. Normally, the immune system eliminates the infection before it spreads. Indeed, most adults who have no history of listeriosis have T lymphocytes primed specifically by Listeria antigens. If the immune system is compromised, however, systemic disease may develop. Listeria monocytogenes multiplies not only extracellularly but also intracellularly within macrophages after phagocytosis and even within parenchymal cells which are entered by induced phagocytosis. It therefore belongs to the large group of facultatively intracellular pathogens (Table 16-1).
Survival within the phagosomes and eventual escape into the cytoplasm are mediated by a toxin, which also acts as a hemolysin. This toxin is one of the so-called SH-activated hemolysins, which are produced by a number of different bacteria such as serogroup A streptococci, pneumococci, and Clostridium perfringens. Obviously, nature has preserved the genetic code for this bacterial product in several species, and consequently the hemolysins from these different bacteria have common biochemical, biologic, and antigenic properties. Nonhemolytic variants of L monocytogenes are completely avirulent, as are the nonhemolytic species L innocua and L welshimeri. Hemolysin is not the only Listeria virulence factor, however, since the hemolytic Listeria species besides L monocytogenes (i.e., L seeligeri and L ivanovii) possess rather limited pathogenicity. The hemolysin gene is located on the chromosome within a cluster of other virulence genes which are all regulated by a common promotor. These additional genetic determinants are necessary for further steps in the intracellular life cycle of L monocytogenes. One particular gene product promotes the polymerization of actin, a component of the host cell cytoskeleton, on the bacterial surface. In this peculiar environment within host cells, surrounded by a sheet of actin filaments, the bacteria reside and even multiply. The growing actin sheet functions as a propulsive force which drives the bacterium across the intracellular pathways until it finally reaches the surface. Then, the host cell is urged to form slim, long protrusions containing living L. monocytogenes. Those cellular projections are engulfed by adjacent cells, even by non-professional phagocytes such as parenchymal cells. By such a mechanism a direct cell-to-cell spread in an infected organ may occur without an extracellular stage.
Note the granulomatous reaction characterized by central accumulation of epitheloid cells (macrophages) and the presence of some dark, round cells (lymphocytes) in the periphery.
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Listeria species are found in living and nonliving matter. Various foodstuffs of vegetable and animal origin are sources of infection. Animal and human carriers also have been described. Most human cases of listeriosis develop in immunocompromised hosts: newborns, old people, cancer patients, and transplant recipients. Reports of sporadic cases of listeriosis are becoming more frequent as the number of persons at risk, especially because of immunosuppression by medical therapy, increases. Outbreaks of listeriosis are due mainly to a common source of contaminated food.
Listeriosis also may be transmitted congenitally across the placenta. The immunocompetent mother suffers at worst a brief, flu-like febrile illness, but the fetus, whose defense system is still immature, becomes seriously ill. Depending on the stage of gestation, the fetus is either stillborn or born with signs of congenital infection. Typically, multiple pyogenic foci are found in several organs (granulomatosis infantiseptica). The onset of listeriosis is delayed (i.e., a few days after birth) when infection is acquired during labor by bacteria colonizing the genital tract of the mother.
Listeria monocytogenes is implicated when monocytosis is observed in the peripheral blood as well as the cerebrospinal fluid. Early diagnosis may be obtained by finding pleocytosis with Gram-positive rods in a Gram stain of smears of the cerebrospinal fluid. Final proof is obtained by culture. Serologic tests are highly unreliable.
Hygienic food processing and storage may reduce the risk of listeriosis. Individuals in high-risk groups (i.e., immuno-compromised individuals and pregnant women) should avoid uncooked food or should at least marinate salads for a long time in a vinegar-based dressing to kill adherent bacteria.
Since a cell-mediated immune response (the most potent weapon against L monocytogenes) is induced only by injection of living antigen, vaccination is difficult. Even an attenuated living vaccine is dangerous for persons with impaired defenses, the proper target group. Completely avirulent live bacteria do not trigger an effective, cell-mediated immune response.
Antimicrobial agents are the mainstay of treatment. Most of the common antibiotics, except cephalosporins, are active against L monocytogenes in vitro. In practice, ampicillin combined with an aminoglycoside has given the best results. However, because infection occurs mainly in infirm patients and because intracellular bacteria are hardly accessible to most drugs, the cure rate is low. Furthermore, Listeria cells, although inhibited, are not killed by ampicillin. High doses for prolonged periods are indicated.
