What Is Listeria Monocytogenes?

Listeria monocytogenes is a Gram-positive bacterium, in the division Firmicutes, named for Joseph Lister. It is motile by means of flagella. Some studies suggest that 1 to 10% of humans may carry L. monocytogenes in their intestines.

Researchers have found L. monocytogenes in at least 37 mammalian species, both domesticated and feral, as well as in at least 17 species of birds and possibly in some species of fish and shellfish. Laboratories can isolate L. monocytogenes from soil, silage, and other environmental sources. L. monocytogenes is quite hardy and resists the deleterious effects of freezing, drying, and heat remarkably well for a bacterium that does not form spores. Most L. monocytogenes are pathogenic to some degree.

Infection by L. monocytogenes causes the disease listeriosis. The manifestations of listeriosis include septicemia, meningitis (or meningoencephalitis), encephalitis, and intrauterine or cervical infections in pregnant women, which may result in spontaneous abortion (2nd/3rd trimester) or stillbirth. Influenza-like symptoms, including persistent fever, usually precede the onset of the aforementioned disorders. Gastrointestinal symptoms such as nausea, vomiting, and diarrhea may precede more serious forms of listeriosis or may be the only symptoms expressed. Gastrointestinal symptoms were epidemiologically associated with use of antacids or cimetidine. The onset time to serious forms of listeriosis is unknown but may range from a few days to three weeks. The onset time to gastrointestinal symptoms is unknown but probably exceeds 12 hours.

The infective dose of L. monocytogenes is unknown but probably varies with the strain and with the susceptibility of the victim. From cases contracted through raw or supposedly pasteurized milk, one may safely assume that in susceptible persons, fewer than 1,000 total organisms may cause disease. L. monocytogenes may invade the gastrointestinal epithelium. Once the bacterium enters the host's monocytes, macrophages, or polymorphonuclear leukocytes, it becomes blood-borne (septicemic) and can grow. Its presence intracellularly in phagocytic cells also permits access to the brain and probably transplacental migration to the fetus in pregnant women. The pathogenesis of L. monocytogenes centers on its ability to survive and multiply in phagocytic host cells.

L. monocytogenes has been associated with such foods as raw milk, supposedly pasteurized fluid milk, cheeses (particularly soft-ripened varieties), ice cream, raw vegetables, fermented raw-meat sausages, raw and cooked poultry, raw meats (of all types), and raw and smoked fish. Its ability to grow at temperatures as low as 3°C permits multiplication in refrigerated foods.

When listeric meningitis occurs, the overall mortality may reach 70%; from septicemia 50%, from perinatal/neonatal infections greater than 80%. In infections during pregnancy, the mother usually survives. Reports of successful treatment with parenteral penicillin or ampicillin exist. Trimethoprim-sulfamethoxazole has been shown effective in patients allergic to penicillin.

The methods for analysis of food are complex and time-consuming. The present FDA method, revised in September, 1990, requires 24 and 48 hours of enrichment, followed by a variety of other tests. Total time to identification takes from 5 to 7 days, but the announcement of specific nonradiolabled DNA probes should soon allow a simpler and faster confirmation of suspect isolates.

Recombinant DNA technology may even permit 2-to-3 day positive analysis in the future. Currently, the FDA is collaborating in adapting its methodology to quantitate very low numbers of the organisms in foods.

Joseph Lister, 1st Baron Lister (April 5, 1827-February 10, 1912) was a famous British surgeon who promoted the idea of sterile surgery while working at the Glasgow Infirmary. He came from a prosperous Quaker home in Upton, Essex.

At the age of 25 he became a Bachelor of Medicine and entered the Royal College of Surgeons. In 1854, Lister became first assistant surgeon to James Syme (1799-1870), a leader of surgery in England. The two became close friends and Lister ended up marrying Syme's daughter Agnes, leaving the Quakers because his religion did not permit alliances with nonmembers.

After six years he got a professorship of surgery at Glasgow. At the time the usual explanation for wound infection was that the exposed tissues were damaged by chemicals in the air or via a stinking "miasma" in the air. The sick wards actually smelled bad, not due to a "miasma" but due to the rotting of wounds. Hospital wards were occasionally aired out at midday but Florence Nightingale's doctrine of fresh air was still science fiction then. Facilities for washing hands or the patient's wounds did not exist and it was even considered unnecessary for the surgeon to wash his hands before he saw a patient. This was strange because the work of Ignaz Philipp Semmelweis and Oliver Wendell Holmes were not heeded even though the parallel should have been obvious.

Lister became aware of a paper published by Louis Pasteur which showed that rotting and fermentation could occur without any oxygen if micro-organisms were present. Lister confirmed this with his own experiments. If micro-organisms were causing gangrene, the problem was how to get rid of them. Pasteur suggested three methods: to filter them out, to heat them up, or expose them to chemical solutions. The first two were inappropriate in a human wound so Lister experimented with the third.

Carbolic acid (phenol) had been in use as a means of deodorising sewage, so Lister tested the results of spraying instruments, the surgical incisions, and dressings with a solution of it. Lister found that carbolic acid solution swabbed on wounds markedly reduced the incidence of gangrene and subsequently published a series of articles on the Antiseptic Principle of the Practice of Surgery describing this procedure on March 16, 1867 in the journal The Lancet.

He also made surgeons wear clean gloves and wash their hands before and after operations with 5% carbolic acid solutions. Instruments were also washed in the same solution and assistants sprayed the solution in the operating theatre.

Many of his contemporaries laughed at him but Lister was said to have never bothered to reply and only heaved an occasional sigh at the world's stupidity. His critics still believed in the theory of spontaneous generation.

Lister left Glasgow in 1869 returning to Edinburgh as successor to Syme as Professor of Surgery,at Edinburgh University and continued to develop improved methods of antisepsis and asepsis,]. His fame had spread by then and audiences of 400 often came to hear him lecture. He moved to King's College in London and became the second man in England to operate on a brain tumour. He also developed a method of repairing kneecaps with metal wire and improved the technique of mastectomy. His discoveries were greatly praised and he was made Baron Lister of Lyme Regis and became one of the twelve original members of the Order of Merit.

Lister retired from practice after his wife, who had long helped him in research, died in 1893 during one of the few vacations they allowed themselves. Studying and writing lost appeal for him and he sank into religious melancholy. Despite suffering a stroke, he still came into the public light from time to time. Edward VII came down with appendicitis two days before his coronation. The surgeons did not dare operate without consulting England's leading surgical authority. The king later told Lister "I know that if it had not been for you and your work, I wouldn't be sitting here today".

A British Institution of Preventive Medicine, previously named after Edward Jenner was renamed in 1899 in honour of Lister.

Two postage stamps were issued in September 1965 to honour Lister for his contributions to antiseptic surgery.

As the germ theory of disease became more widely accepted, it was realised that infection could be better avoided by preventing bacteria from getting into wounds in the first place. This led to the rise of sterile surgery. Some consider Lister the father of modern antisepsis.

Listerine mouthwash is named after him for his work in antisepsis.

He credited Ignaz Semmelweis for earlier work in antiseptic treatment: "Without Semmelweis, my achievements would be nothing."

Listeriosis is an bacterial infection caused by a gram-positive motile bacterium, Listeria monocytogenes. Listeriosis is relatively rare and occurs primarily in newborn infants, elderly patients, and patients who are immunocompromised.

Epidemiology Incidence is 7.4 cases per million population. Annually, 1850 cases are reported in the US. Pregnant women account for 27% of all cases. Of all nonperinatal infections, 70% occur in immunocompromised patients.

Pathophysiology L monocytogenes is ubiquitous in the environment. The main route of acquisition of Listeria is through the ingestion of contaminated food products. Listeria has been isolated from raw meat, dairy products, vegetables, and seafood. Soft cheeses and unpasteurized milk have been the most frequently culprits.

Features There are four distinct clinical syndromes:

Infection in pregnancy: Listeria can proliferate asymptomatically in the vagina and uterus. If the mother becomes symptomatic, it is usually in the third trimester. Symptoms include fever, myalgias, arthralgias and headache. Abortion, stillbirth and preterm labor are complications of GU infection. Neonatal infection (granulomatosis infantisepticum): There are two forms. One, an early-onset sepsis, with Listeria acquired in utero, results in premature birth. Listeria can be isolated in the placenta, blood, meconium, nose, ears, and throat. Another, late-onset meningitis is acquired through vaginal transmission, although it also has been reported with cesarean deliveries. CNS infection: Listeria has a predilection for the brain parenchyma, especially the brain stem, and the meninges. Mental status changes are common. Seizures occur in at least 25% of patients. Cranial nerve palsies, encephalitis, meningitis and abscesses occur. Gastroenteritis: L monocytogenes can produce food-borne diarrheal disease, which typically is noninvasive. The median incubation period is 1-2 days, with diarrhea lasting anywhere from 1-3 days. Patients present with fever, myalgias, and diarrhea. Diagnosis L monocytogenes can often be cultured from the blood, and always cultured from the CSF. There are no reliable serological or stool tests.

Treatment Bacteremia should be treated for 2 weeks, meningitis for 3 weeks, and brain abscess for at least 6 weeks. Ampicillin generally is considered the preferred agent, but other agents may be acceptable. Gentamicin is added frequently for synergy.

Prognosis The overall mortality rate is 20-30%. Of all pregnancy-related cases, 22% resulted in fetal loss or neonatal death, but mothers usually survive.

Prevention Recommended by the CDC:
Cook all raw food thoroughly. Wash raw vegetables. Avoid consumption of raw milk or milk products. Wash hands, knives, and cutting boards after handling uncooked foods. For pregnant or immunocompromised patients, avoid soft cheeses (eg, feta, Brie, Camembert, bleu). Cream cheese, yogurt, and cottage cheese are allowed. Reheat leftover or ready-to-eat foods (eg, hot dogs) until steaming hot. Avoid delicatessen foods unless they are thoroughly reheated.

What is Listeria monocytogenes? Listeria monocytogenes (Listeria) is a pathogenic (disease-causing) bacterium that is food borne and causes an illness called listeriosis1. It is frequently overlooked as a possible cause of illness due to its unique growth capabilities. First, it is somewhat difficult for laboratories to grow, and when they do so, Listeria can be confused with common harmless contaminants and disregarded. Second, most bacteria grow poorly when temperatures fall below 40°F, while Listeria survives in temperatures from below freezing (20°F) to body temperature and it grows best at 0°F to 50°F,1 including the temperature range that we use for refrigeration. As a result, Listeria may be transmitted in ready-to-eat foods that have been kept properly refrigerated. Its ability to grow in such diverse environments is just one of the many challenges presented by this dangerous bacterium.

It is estimated that Listeria causes approximately 1,600 cases of listeriosis annually, resulting in 415 deaths.2

Where does Listeria monocytogenes come from? There are many opportunities for contamination with Listeria during the process of food production because Listeria monocytogenes is ubiquitous in the environment.1 For example, it can be grown from wild and domestic animals, birds, insects, soil and wastewater, and vegetation. As it is a bacterium found in soil and vegetation, it is easily contracted and transmitted by herd animals. Listeria is found in grazing areas, stale water supplies, and poorly prepared animal feed. It can live in the intestines of humans, animals, and birds for long periods of time without causing infection. The bacterium is often isolated in cattle, sheep, and fowl, and is also found in dairy products, fruits, and vegetables.

What are the symptoms of infection with Listeria monocytogenes? It is believed that ingestion of as few as 1,000 cells of Listeria bacteria can result in illness. After ingestion of food contaminated with Listeria, incubation periods for infection are in the range of 3 to 70 days, usually 4 to 21 days.3

Five days to three weeks after ingestion, Listeria has access to all body areas and may involve the central nervous system, heart, eyes, or other locations.4 Fetuses of pregnant women are particularly vulnerable to the Listeria bacterium. A person with listeriosis usually has fever, muscle aches, and gastrointestinal symptoms such as nausea or diarrhea. If infection spreads to the nervous system, symptoms such as headache, stiff neck, loss of balance, confusion, obtundation or convulsions can occur. With brain involvement, listeriosis may mimic a stroke.

Infected pregnant women will ordinarily experience only a mild, flu-like illness; however, infection during pregnancy can lead to miscarriage, infection of the newborn, or even stillbirth.5 The perinatal and neonatal mortality rate is 80%.4

Human cases of Listeria are, for the most part, sporadic and treatable. Nonetheless, Listeria remains an important threat to public health, especially among those most susceptible to this disease. With the increase of the numbers of immunocompromised people, the risk multiplies. The fact that Listeria is a disease easily transmitted from mother to fetus through the placenta is worrisome to an expectant mother, especially since pregnant women themselves rarely show outward signs of such a devastating infection.

The public isn't the only group that should learn more about Listeria. Many doctors overlook the possibility of Listeria food poisoning, because they do not know that Listeria can survive and grow in refrigerated foods. For example, a recent nationwide outbreak of Listeria poisoning was eventually determined to have been caused by contaminated hot dogs and lunchmeat - foods that had not previously been considered dangerous. More research needs to be done, so that all of the mechanisms and intricacies of this bacterial strain might be understood. Above all, common myths about "proper" food storage need to be updated, so that contamination can be kept at a minimum. A blood test is typically the most reliable way to find out if your symptoms are due to listeriosis, particularly during pregnancy.

Listeriosis Listeriosis is the disease caused by Listeria monocytogenes. It is acquired by the ingestion of contaminated foods. Certain groups of individuals are at great risk for listeriosis. These are pregnant women (and their unborn children) and immunocompromised persons (e.g., transplant recipients). Among infants, listeriosis occurs when the infection is transmitted from the mother, either through the placenta or during the birthing process. These host factors, along with the amount of bacteria ingested and the virulence of the strain, determine the risk of disease.

Listeria can invade the body through a normal and intact gastrointestinal tract. Once in the body Listeria bacteria can travel through the blood stream, but are often found inside cells (they are "intracellular" pathogens). Listeria can co-opt the cell's machinery to its own advantage by manipulating the host cell genes, and then move directly from cell-to-cell, avoiding many of the host's defense mechanisms5. The bacteria also produce toxins that damages cells.

For unknown reasons, in immune-deficient hosts Listeria invades and grows best in the central nervous system, causing meningitis and/or encephalitis (brain infection). In pregnant women, the fetus is most heavily infected, leading to spontaneous abortion, stillbirths, or sepsis in infancy.

Every year in the U.S. approximately 2,500 cases of Listeriosis are known to occur. (It is likely that more cases go unrecognized). About 500 deaths per year are attributed to listeriosis.

How do you know if you have Listeriosis? Symptoms of such as fever and stiff neck could be the result of a listeriosis infection. If you have these symptoms, consult your doctor, who can do a blood or spinal fluid test that will show if you have listeriosis. A blood test is typically the most reliable way to find out if your symptoms are due to listeriosis, particularly during pregnancy.

Do antibiotics treat Listeria monocytogenes? Because it is a bacterium, there are several antibiotics with which Listeria may be treated. The antibiotics that have the most activity are ampicillin, gentamicin, and trimethoprim/sulfamethoxizole (Bactrim®, Septa®).8

When infection occurs during pregnancy, antibiotics given promptly to the pregnant woman can often prevent infection of the fetus. Babies with listeriosis receive the same antibiotics as adults, although a combination of antibiotics is often used until physicians are certain of the diagnosis.

Even with prompt treatment, some infections result in death. This is particularly likely in those with central nervous system involvement, the elderly and in persons with other serious medical problems

8. Gilbert DN, Moellering RC, Sande MA. The Sanford Guide to Antimicrobial Therapy 2001. Antimicrobial, Inc, Hyde Park, VT, 2001.

Who is most susceptible to Listeria monocytogenes? Listeriosis is avoided by altering dietary habits. While the general public need not be concerned, persons at risk need to be informed of that risk and take the proper precautions.

The body's defense against Listeria monocytogenes and other intracellular pathogens is called "cell-mediated immunity" because it depends on our cells (as opposed to our antibodies), especially lymphocytes called "T-cells." Therefore, it is not surprising that individuals whose cell-mediated immunity is suppressed are more susceptible to the devastating effects of Listeriosis.

Pregnant women naturally have a depressed cell-mediated immune system; many think that this occurs so that the mother's immune system will not reject the fetus. The immune systems fetuses and newborns are very immature; they are extremely susceptible to intracellular pathogens. Other adults, especially transplant recipients and lymphoma patients, are given necessary therapies with the specific intent of depressing immune T-cells, and these individuals become especially susceptible to Listeria monocytogenes as well.

Pregnant women are about 20 times more likely than other healthy adults to get listeriosis. About one-third of listeriosis cases happen during pregnancy. The incidence of listeriosis in the newborn is 8.6 per 100,000 live births.9 There is no routine screening test for susceptibility to listeriosis during pregnancy, as there is for rubella and some other congenital infections. Newborns, rather than the pregnant women themselves, suffer the serious effects of infection in pregnancy. Persons with weakened immune systems due to treatment, particularly transplant recipients10 and persons on treatment for lymphoma, but also other cancer victims, are at significantly increased risk for Listeria infection.

· Persons with AIDS suffer listeriosis 65-145 times more frequently than the general population.11

· Persons who take glucocorticosteroid medications (also called cortisone) are also at increased risk.10 The most common medication prescribed in this class is prednisone. The threshold above which prednisone begins to have a significant effect on the immune system is 20 mg per day for 5 days.

· The elderly and certain debilitated patients (such as those on dialysis or alcoholics) are at minor increased risk for listeriosis.

How can a Listeria monocytogenes infection be prevented?

Ready-to-eat foods provide a risk of transmitting Listeria, some more than others. Although this information is available to the public11,12 a conscientious health care provider rendering care for an at-risk individual should point this information out.

· Avoid soft cheeses10 such as feta, Brie, Camembert, blue-veined, and Mexican-style cheese. (Hard cheese, processed cheeses, cream cheese, cottage cheese, or yogurt need not be avoided.)

· Cook leftover foods or ready-to-eat foods,10 such as hot dogs, until steaming hot before eating.

· Undercooked chicken has also been associated with listeriosis.10 To make chicken safe from bacterial pathogens the thickest section (the center of the breast) should reach 165°F.

· Recently, uncooked fish, whether smoked or not, has been identified as source of Listeria monocytogenes.13,14 Smoked trout, "gravad" fish, sushi, sashimi, and cerviche and such uncooked fish should also be avoided by individuals at risk.

In the hazard identification, the known or potential health effects associated with Listeria monocytogenes are identified by establishing the general relationship between the pathogen, its presence in foods, and the adverse outcome (illness or death) associated with consumption of foods contaminated with Listeria monocytogenes. While the negative health impact of a hazard must be recognized for a risk assessment to be undertaken, the nature of the impact must be clearly defined, and specific endpoints, or health outcomes of interest, identified. Common endpoints for infectious agents are infection, disease (morbidity), death, and chronic sequelae (long-term after-effects). This risk assessment is concerned with the endpoints of serious illness and death.

Listeria monocytogenes Listeria are short (0.5 mm in diameter by 1 to 2 mm long) gram positive, non-spore-forming rods. Listeria monocytogenes is one of six species are currently recognized within the genus (Rocourt, 1999). It can be isolated from numerous species of domestic and wild animals, as well as from soil, silage, and other environmental sources. Listeria monocytogenes can be classified into a number of subtypes using several methods. The most common is based upon recognition of antigens on the surface of the bacterium by specific antisera (Graves et al., 1999). Thirteen of these serotypes are associated with Listeria monocytogenes (1/2a, 1/2b, 1/2c, 3a, 3b, 3c, 4a, 4ab, 4b, 4c, 4d, 4e, 7). Some of these serotypes are also associated with other species of Listeria (1/2b, 4ab, 4c, 4d). The numbers and letters refer to specific combinations of bacterial antigens used for serotyping (Seeliger and Höhne, 1979). Serotyping is often used as a first step to type strains associated with human listeriosis, but it has relatively low discriminating power compared to molecular methods such as ribotyping or pulse field gel electrophoresis (PFGE). Ribotyping relies on separation and analysis of specific well-conserved DNA fragments and this method is often used in combination with serotyping to identify and trace a specific strain of Listeria monocytogenes associated with illness to a food source or to link seemingly unrelated illnesses. On the basis of ribotyping and PCR-restriction fragment length polymorphism of three virulence genes (hly, actA, and inlA), Wiedmann et al. (1997) separated Listeria monocytogenes into three lineages, which appear to have distinctive pathogenicities. Several reviews and books have summarized the ecology, characteristics, presence in foods, and public health effects of Listeria (Farber et al., 1996; Farber and Peterkin, 1991; Ryser, 1999a; Slutsker and Schuchat, 1999).

Listeriosis Listeria monocytogenes is a well-known hazard for which there is extensive surveillance and outbreak data. Although rare when compared to many other foodborne diseases (Table II-1), listeriosis often leads to severe consequences, particularly in susceptible subpopulations. In 2000, Listeria monocytogenes caused higher rates of hospitalization than any other pathogen and caused over one-third of the reported deaths. Because listeriosis so often results in medical care, CDC believes that its surveillance system (FoodNet) misses only half of all cases, compared with 97% of missed cases for other pathogens (Mead et al., 1999). A description of the Foodborne Diseases Active Surveillance Network (FoodNet) is provided in Appendix 4. Listeria monocytogenes usually causes only flu-like symptoms in healthy people. For the purposes of this risk assessment, a distinction is made between non-invasive listeriosis with mild, flu-like symptoms (referred to as listerial gastroenteritis) and invasive listeriosis that is severe and sometimes life-threatening (referred to as listeriosis in the risk assessment).

Invasive listeriosis typically has a 2 to 3 week incubation time, but can sometimes extend up to three months (Gellin and Broome, 1989). Serious conditions caused by Listeria monocytogenes in adults can include septicema, meningitis, enceplalitis, abortion, or stillbirth (Shelef, 1989a). Invasive diseases in nonpregenant adults can include a variety of other clinical manifestations. Endocarditis can occur in patients with underlying cardiac lesions. Cutaneous infections have been reported in persons handling animals and those exposed by accidental exposure while working in laboratories. Focal infections are rare but can include endophthalmitis, septic arthritis, osteomyelitis, pleural infection and peritonitis (Slutsker and Schuchat, 1999).

Most information on the pathogenesis of Listeria monocytogenes comes from studies in mice or cell biology studies using tissue culture cells (Kuhn and Goebel, 1999). When ingested, Listeria monocytogenes penetrates the intestinal tissue and is exposed to phagocytic cells of the immune system that function to kill microbial invaders. A portion of invading Listeria monocytogenes can evade the killing mechanisms, survive, and multiply within host phagocytes (macrophages). Protected within, or having escaped from these host cells, Listeria monocytogenes moves throughout the host via blood or lymphatic circulation to various tissues. Once in a tissue it can invade cells, multiply within them, and then use cytoskeletal acting filaments to spread to adjacent cells, without risk of exposure to humoral components of the immune system. The probability of tissue invasion depends upon the number of organisms consumed, host susceptibility, and virulence of the strain (Gellin and Broome, 1989). Most cases of listeriosis occur in fetuses or neonates and individuals with a predisposing condition that impairs the immune system (Slutsker and Schuchat, 1999).

Although Listeria monocytogenes is generally known to cause severe illness, there have been outbreaks in which the majority of patients only developed mild symptoms such as diarrhea, fever, headache, and myalgia (Dalton et al., 1997; Salamina et al., 1996; Riedo et al., 1994; Aureli et al., 2000). The frequency of these types of outbreaks is unknown because most cases of listerial gastroenteritis are not reported to public health officials. For this reason, this risk assessment is restricted to severe cases of listeriosis.

High Risk Individuals Two high risk (susceptible) subpopulations are considered in this risk assessment: elderly and perinatal. Persons at high risk for developing listeriosis often have deficient or immature immune systems (immunocompromised). Actual numbers of susceptible individuals are difficult to determine because these individuals belong to diverse groups including the elderly, cancer and transplant patients, and persons with immunosuppressive diseases such as AIDS (Morris and Potter, 1997). In addition, the description of an immunocompromised state is often based on qualitative or circumstantial criteria that may apply to some, but not all members of a particular group.

Susceptible subpopulations are not homogeneous with regard to susceptibility, both within and between groups. High-risk subpopulations can be separated into non-perinatal and perinatal groups. A non-pregnancy related case is a person other than a pregnant woman or her child in whom Listeria monocytogenes organisms are cultured from a normally sterile site. Of the non-perinatal groups, the elderly constitute the largest and most well characterized subpopulation. A case-control study revealed that of 98 cases of non-perinatal sporadic listeriosis in the United States, 98% had at least one underlying medical condition. Most (69%) of these were associated with probable immunosuppression (Schuchat et al., 1992). The next largest group (33%) was associated with heart disease. Many individuals fell under more than one category. In people over the age of 60, the disease is often present with sepsis or meningitis (Schuchat et al., 1991; Shelef, 1989a; Linnan et al., 1988; WHO Work Group, 1988).

A perinatal infection occurs primarily as the result of transplacental transmission to the fetus following infection of the mother. The perinatal group includes fetuses or neonates from whom Listeria monocytogenes organisms are isolated from a normally sterile body site. Perinatal infections can occur before or after birth and outcomes include live birth of an infected neonate, stillbirth, or premature termination of pregnancy. Neonates (newborns) are defined by the American Medical Association as newborn infants from birth to one month of age. In this risk assessment, neonates are considered to be between 0-30 days of age. The term fetus is used to refer to an unborn child from 16 weeks after fertilization to birth.

Women may become infected with Listeria monocytogenes at any time during pregnancy, but most cases of listeriosis are reported in the third trimester (Slutsker and Schuchat, 1999). Usually three to seven days after the onset of symptoms, a woman may abort the fetus or have premature delivery (Gellin and Broome, 1989). In the first trimester, listeriosis may result in spontaneous abortion. In later stages of pregnancy, the result may be stillbirth or birth of a critically ill newborn. Listeriosis is rarely life threatening to the mother and is not known to cause increased risk in subsequent pregnancies (Skidmore, 1981; Farber and Peterkin, 1991).

Neonates may present with an early-onset or late-onset form of listeriosis. Approximately 45 to 70% of newborn cases are early-onset (Slutsker and Schuchat, 1999). Early-onset listeriosis often presents with sepsis and may progress to a syndrome known as granulomatosis infantisepticum (Gellin and Broome, 1989). This syndrome is often characterized by widely disseminated granulomas, premature birth, respiratory distress, and circulatory failure. Late-onset is defined as listeriosis in a newborn between 8 to 30 days of life. Usually late-onset neonates are born apparently healthy and at full-term. Meningitis rather than sepsis is more common in late-onset neonates (Farber, 1991a). The mothers of late-onset neonates usually have an uneventful pregnancy without illness. Listeria monocytogenes is rarely isolated from the mother and the source of listeriosis is often not identified in late-onset cases (Farber and Peterkin, 1991; Slutsker and Schuchat, 1999).

Non-Invasive Listeriosis (Listerial Gastroenteritis) Gastrointestinal illness (listerial gastroenteritis) from Listeria monocytogenes has only recently been recognized as a distinct entity (Dalton et al., 1997). Typical signs and symptoms associated with the mild form of Listeria monocytogenes infection are primarily those associated with gastrointestinal illness: chills, diarrhea, headache, abdominal pain and cramps, nausea, vomiting, fatigue, and myalgia. A variety of foods have been implicated as the vehicle of infection. Because symptoms are mild, there is a high potential for underreporting of listerial gastroenteritis. Data are currently unavailable through foodborne surveillance mechanisms such as FoodNet to capture the incidence of listerial gastroenteritis since routine stool cultures do not include evaluation for Listeria monocytogenes.

Nevertheless, outbreaks of listerial gastroenteritis have been identified. Table II-2 shows reported events where most of the cases reported mild symptoms (Heitmann et al., 1997; Dalton et al., 1997; Salamina et al., 1996; Riedo et al., 1994; Aureli et al., 2000). In the vast majority of these cases, there was no evidence for invasive disease beyond the intestine. Gastrointestinal and other mild symptoms were reported in individuals with no known underlying predisposition. In two of these reports, there was evidence of very high levels of food contamination. These facts suggest that, in normal individuals, listerial gastroenteritis may be associated with exposure to high levels of Listeria monocytogenes. It is possible that this manifestation of Listeria monocytogenes infection is a different disease compared to invasive and more severe listeriosis. Because modeling in this risk assessment depends on case reporting and non-invasive gastroenteritis is not likely to be reported, listerial gastroenteritis was not considered in the risk assessment model. However, the outbreaks do provide important observations related to the exposure of populations to extremely high levels of the microorganisms without identifiable cases of invasive listeriosis.

Listeriosis is a disease caused by the bacteria Listeria monocytogenes. It is rare, but when it does occur, it most frequently affects pregnant women, newborns, and children and adults whose immunity is weakened by diseases such as cancer or AIDS. People who have had transplants are also more at risk for listeriosis.

Listeria may be transmitted through food, soil, and water and has caused local outbreaks. There have been documented cases of its transmission through a variety of items: deli meats and cold cuts, soft-ripened cheese, milk, undercooked chicken, uncooked hot dogs, shellfish, and coleslaw made from contaminated cabbage. Many cases of infection, however, have no identifiable source.

If a pregnant woman is a rectal or vaginal carrier of Listeria bacteria (meaning she is infected with Listeria, but does not have symptoms), her newborn could become infected at the time of delivery. She could also transmit the infection to the fetus across the placenta. Fortunately, newborns are rarely infected with Listeria.

According to the Centers for Disease Control and Prevention, about 2,500 people in the United States develop listeriosis each year. About 20% of people with listeriosis die from the infection.

Signs and Symptoms Listeria infection can cause a variety of serious illnesses, including pneumonia, meningitis, and sepsis, a severe, generalized blood-borne infection. Signs and symptoms of serious infection may include fever, difficulty breathing, poor feeding, vomiting, diarrhea, lethargy, and irritability. It is most often seen in very young infants, the elderly, and patients whose immune systems have been weakened. Pregnant women who develop listeriosis may experience only a mild, flu-like illness, although premature delivery may occur because of the infection.

Contagiousness Listeriosis generally is not contagious from person to person, however, it can be transmitted from a pregnant woman to her fetus.

Incubation A newborn infant may be born with the disease. If acquired at birth, the incubation period is 7 to 28 days.

For older babies and children, it may take up to 3 weeks for a child to become ill after ingesting the Listeria bacteria. The average incubation period is reported to be 31 days with a range from 11 to 47 days.

Treatment Listeriosis is a serious disease requiring hospitalization. A combination of antibiotics is given intravenously through a small straw-like catheter that is inserted into a vein. The duration of antibiotic treatment is at least 2 weeks.

Duration If an unborn fetus becomes infected with Listeria, miscarriage, stillbirth, or premature delivery can result. If a newborn becomes infected with the bacteria at birth, quick, thorough treatment with antibiotics will usually cure the infection within a couple of weeks.

Children whose immune systems are compromised by illness or infection, such as cancer or AIDS, are more likely to develop severe listeriosis infections, which are more difficult to treat.

In all cases of listeriosis, the earlier the detection and treatment, the better the chances of survival.

Prevention Although there are no vaccines against Listeria monocytogenes, it's recommended that you follow food safety guidelines to prevent your family from becoming infected with the bacteria:

Always cook food (especially meat and eggs) thoroughly to the proper internal temperature. Wash fruits and vegetables thoroughly before eating. Avoid foods made from unpasteurized milk. Avoid soft cheeses such as feta, Brie, and Camembert and blue-veined and Mexican-style cheeses if you're pregnant or during childhood. Reheat precooked, prepackaged foods - such as deli meats or hot dogs - to steaming hot temperatures, especially if you're pregnant.

Listeriosis is caused by an infection with the bacterium Listeria monocytogenes. This bacteria can be carried by many animals and birds, and it has been found in soil, water, sewage, and animal feed. Five out of every 100 people carry Listeria monocytogenes in their intestines. Listeriosis is considered a "food-borne illness" because most people are probably infected after eating food contaminated with Listeria monocytogenes. However, a woman can pass the bacteria to her baby during pregnancy. In addition, there have been a few cases where workers have developed Listeria skin infections by touching infected calves or poultry.

Listeria monocytogenes is found in soil and water. Vegetables can become contaminated from the soil or from manure used as fertilizer. Animals can carry the bacterium without appearing ill and can contaminate foods of animal origin such as meats and dairy products. The bacterium has been found in a variety of raw foods, such as uncooked meats and vegetables, as well as in processed foods that become contaminated after processing, such as soft cheeses and cold cuts at the deli counter. Unpasteurized (raw) milk or foods made from unpasteurized milk may contain the bacterium. Persons at risk can prevent Listeria infection by avoiding certain high-risk foods and by handling food properly. Listeria is killed by pasteurization, and heating procedures used to prepare ready-to-eat processed meats should be sufficient to kill the bacterium. However, unless good manufacturing practices are followed, contamination can occur after processing. How do you get listeriosis? You get listeriosis by eating food contaminated with Listeria. j, k. Babies can be born with listeriosis if their mothers eat contaminated food during pregnancy. Although healthy persons may consume contaminated foods without becoming ill, those at increased risk for infection can probably get listeriosis after eating food contaminated with even a few bacteria. Persons at risk can prevent Listeria infection by avoiding certain high-risk foods and by handling food properly.

In the 1980s, the United States government began taking measures to decrease the occurrence of listeriosis. Processed meats and dairy products are now tested for the presence of Listeria monocytogenes. The Food and Drug Administration (FDA) and the Food Safety and Inspection Service (FSIS) can legally prevent food from being shipped, or order food recalls, if they detect any Listeria bacteria. These inspections, in combination with the public education regarding the proper handling of uncooked foods, appear to be working. In 1989, there were 1,965 cases of listeriosis with 481 deaths. In 1993, the numbers fell to 1,092 cases with 248 deaths.

In 1996, the Centers for Disease Control and Prevention (CDC) began a nationwide food-borne disease surveillance program called "FoodNet," in which seven states were participating by January 1997. Results from the program indicated that, in 1996, one person out of every 200,000 people got listeriosis. FoodNet also revealed that the hospitalization rate was higher for listeriosis (94%) than for any other food-borne illness. In addition, FoodNet found that the Listeria bacteria reached the blood and cerebrospinal fluid in 89% of cases, a higher percentage than in any other food-borne illness.

Listeria monocytogenes is a gram positive rod which is found worldwide in animals, plants and soil. L. monocytogenes causes listeriosis [meningitis and bacteraemia (infection of blood)] in children and in adults with weakened immune systems. Listeriosis can also be contracted from eating contaminated foods (eg. unpasteurized cheese, prepared salads and manufactured meats), or from contact with infected animals or their faeces and can lead to abortion or premature delivery in pregnant women (abortion and stillbirth), meningitis in newborn babies and bacteraemia or meningitis in adults. For diagnosis, the bacterium can be isolated and grown from the patient and is identified by specific growth conditions.

Listeria

A highly publicized national outbreak of Listeria monocytogenes has focused attention and raised awareness of this relatively uncommon but potentially serious foodborne infection. Physicians can reduce the morbidity and mortality of Listeria infections in several ways including: 1) Educating patients at high risk for illness about Listeriosis and precautions they can take to reduce their risk 2) Considering Listeria in the differential in appropriate individuals and promptly initiating therapy 3) Promptly notifying the WCDH of any cases of Listeriosis - this will result in an investigation and possible identification of contaminated a food source. Timely recalls of such foods can prevent others from becoming ill. 4) Having all clinical isolates of Listeria for molecular typing (DNA fingerprinting). The WCDH can facilitate or arrange this if notified. Molecular typing can identify outbreaks and food sources when there are relatively few cases which occur over longer periods of time and a wide geographical distribution. Two recent outbreaks which otherwise may have gone undetected were identified in this manner.

Outbreaks

Beginning August 1998, an outbreak involving 17 states, including New York has resulted in about 80 cases and 15 deaths. Five of the deaths have been miscarriages - fetuses or infants of pregnant women infected with Listeria. This outbreak has been linked to contaminated hot dogs and deli meats distributed by the Bil Mar Foods division of Sara Lee and a recall of these contaminated products dates to 22 December 1998. In February 1999, a second outbreak was identified involving 8 cases in 3 states, including New York (NY state cases are in NYC) ,and has been linked to Mragowski cheese which is frequently sold at Polish deli's.

How do you know if you have listeriosis? A person with listeriosis usually has fever, muscle aches, and sometimes gastrointestinal symptoms such as nausea or diarrhea. If infection spreads to the nervous system, symptoms such as headache, stiff neck, confusion, loss of balance, or convulsions can occur. Infected pregnant women may experience only a mild, flu-like illness; however, infection during pregnancy can lead to premature delivery, infection of the newborn, or even stillbirth. There is no routine screening test for susceptibility to listeriosis during pregnancy, as there is for rubella and some other congenital infections. If you have symptoms such as fever or stiff neck, consult your doctor. A blood or spinal fluid test (to cultivate the bacteria) will show if you have listeriosis. l, j, l. During pregnancy, a blood test is the most reliable way to find out if your symptoms are due to listeriosis. Can listeriosis be prevented? The general guidelines recommended for the prevention of listeriosis are similar to those used to help prevent other foodborne illnesses, such as salmonellosis.

Epidemiology

Although no cases of Listeria infections involved in these outbreaks have been identified in Westchester County, 3 of 6 cases of Listeriosis reported during 1998 occurred in pregnant women, and all 3 infections resulted in either pre-term delivery or miscarriage. An average of 4-6 Listeria infections a year are reported annually to the Westchester County Health Department. Prior to 1998, most of the cases occurred in elderly individuals with underlying health problems.

Listeria monocytogenes infections, although much less common (1-2,000 cases/yr in the U.S.), is more serious than other foodborne illnesses, with 25% of cases being fatal. It is thus not a common cause of illness in the general population but can cause life threatening meningoencephalitis and bacteremia in neonates, pregnant women, immunosuppressed individuals, and the elderly. Education regarding Listeria is particularly beneficial to such individuals. Knowledge and awareness of Listeria infections among the general public appears to be much lower than that for other foodborne illnesses, such E.coli 0157:H7. These high-risk individuals are also advised to be alerted to recalls of foods contaminated with Listeria such as those described in more detail below.

Listeria is widespread in nature and found commonly in soil, decaying vegetation, and in the fecal flora of many mammals. Listeria has also been recovered from many foods including unpasteurized dairy products, raw vegetables, meats, poultry, and fish.

Listeria infection may not cause any illness in most individuals or only cause a mild self-limited flu-like illness in pregnant women and frequently be unrecognized. If left untreated during pregnancy, it can lead to premature delivery and fetal death. About 20% of Listeria infections occur in pregnant women and most occur during the third trimester. Meningitis and bacteremia are the most commonly recognized clinical syndromes; it is the fourth most common cause of meningitis in the U.S., one of three major causes of neonatal meningitis, and the leading cause of meningitis in individuals receiving corticosteroids, lymphomas, and organ transplant recipients. Nuchal rigidity is less common (15-20%) but movement disorders, seizures, and fluctuating mental status are more common (20-25%) than with other bacterial meningitides. On exam of CSF, Gram stain is negative and glucose in normal in over half of cases and there is a predominance of mononuclear cells in about one third of cases.

Listeria infection should thus be considered in the differential of high-risk patients presenting with compatible clinical findings. A history of eating any high-risk food items is helpful. High-risk foods include soft cheeses (which are at increased risk of contamination even following pasteurization), particularly those eaten abroad, or undercooked hot dogs.

Diagnosis is established by positive blood cultures, or lumbar puncture and CSF cultures.

Treatment - The recommended treatment for Listeriosis is ampicillin (1.5 - 2.0 gm q 4-6 hrs) and gentamicin (5 mg/kg q 8 hrs) for 2 weeks (if bacteremia only) or 3 weeks (if CNS infection is present). Penicillin, in high doses (3 million units q 4 hrs), or TMP/SMX (20 mg/kg/day) divided into 4 doses, or erythromycin (1 gm q 6 hrs) are alternative regimens which have been used with successful outcomes, although clinical experience with these latter is limited. Gentamicin is generally contraindicated during pregnancy.

How can you reduce your risk for listeriosis? General recommendations: Cook thoroughly raw food from animal sources, such as beef, pork, or poultry. Wash raw vegetables thoroughly before eating. Keep uncooked meats separate from vegetables and from cooked foods and ready-to-eat foods. Avoid raw (unpasteurized) milk or foods made from raw milk. Wash hands, knives, and cutting boards after handling uncooked foods. Recommendations for persons at high risk, such as pregnant women and persons with weakened immune systems: In addition to the recommendations listed above: Avoid soft cheeses such as feta, Brie, Camembert, blue-veined, and Mexican -style cheese. (Hard cheesed, processed cheeses, cream cheese, cottage cheese, or yogurt need not be avoided.) Cook until steaming hot left-over foods or ready-to-eat foods, such as hot dogs, before eating. c, f, j, b, g. Although the risk of listeriosis associated with foods from deli counters is relatively low, pregnant women and immunosupressed persons may choose to avoid these foods or thoroughly reheat cold cuts before eating.

Food Recalls

In response to the outbreak linked to hot dogs and deli meats distributed by Sara Lee, there has been an increased number of foods tested for and found to contain Listeria. Because serotyping testing is not readily available and the infectious inoculum for Listeria is not established, the significance of these findings is not entirely clear but many food manufacturers have recalled their products. Some of the more widely distributed and well known products that have been recalled since January 1999 include Oscar Meyer variety lunchmeats and Thorn Apple Valley hot dogs and lunch meats. Except for the Sara Lee and Mragowski cheese outbreaks described above, NO human illnesses have been identified in association with these products.

Listeria monocytogenes is a Gram-positive, facultatively intracellular bacterium. It causes severe infection both in animals and human. The rates of infection are highest among infants, elderly people, pregnant women and immune-suppressed individuals. Contaminated food (including raw milk, soft cheese) as a source for sporadic and common source-outbreaks of listeriosis has been illustrated. Listeria monocytogenes has special life style, which enables it to escape from phagosome and avoid circulating antibodies.

One of the important clinical features of listeriosis is infection of the central nervous system (CNS). Listeria monocytogenes has special tropism to brain (particularly in the brainstem). The listeria encephalitis in sheep is called circling disease. The neurological lesions are usually confined to the brainstem, especially the pons and medulla oblongata, where the inflammatory cell infiltrates and bacteria are most prevalent in areas corresponding to the sensory trigeminal nuclei. In human, the listeria encephalitis involves the brainstem is called rhombencephalitis. The infection focals can be found in the pons and medulla with MRI. The associated mortality is high and usually have serious sequelae in survivors.

It has been suggested that the listeric encephalitis in sheep results from axonal transport of the bacteria along one or more branches of the trigeminal nerve to the brainstem. Although the mechanisms for bacterial transfer through the blood-brain barrier and targeting to the rhombencephalon have not been clarified, a hematogenous spread of the bacteria has also been suggested.

In spite of the great clinical importance of Listeria monocytogenes infections in the nervous system, its pathogenesis is still unclear. Our project is aim to study how Listeria monocytogenes spread into CNS and how the host innate and adaptive immune response. The experiments have been performed both in vivo and in vitro.

In the natural host, peripheral sensory neurons appear to be a primary target for the bacterial attack. In present study, we use infection of dorsal root ganglia (DRG) primary sensory neurons, as a model to analyze bacterial and neuronal factors of importance for neurovirulence of Listeria monocytogenes. Our lab developed a culture system where DRG neurons can relatively grow free from other cells, and they are effectively infected by listeria monocytogenes. Our preliminary results showed that Listeria monocytogenes can infect both axons and DRG nerve cell bodies, and that the bacteria can migrate in a retrograde as well as anterograde direction. (see the picture)

The model of listeriosis is widely used to study cell-mediated immunity. It showed that Listeria immunity involves different cells participating at different stages, and that multiple cytokines are involved in a co-ordinate series of stages. In our study, different kinds of transgenetic mice and Listeria monocytogenes mutants with deletions in virulence genes are used, to exam the immune factors and bacterial factors involved in the neuroinvasion of Listeria monocytogenes.

Recent recalls of certain meat products resulted from contamination by Listeria monocytogenes, a bacteria which has been found in raw and pasteurized milk, ice cream, certain soft cheeses, poultry, fish, meat, and vegetables. It is the second major bacterial cause of foodborne death after Salmonella but higher than Campylobacter and E. coli. The severity of Listeria food poisoning can cause hospitalization for 90% of cases. As many as 10% of humans may be intestinal carriers of the bacteria. The majority of cases have been attributed to improper food handling, cooking, or storage in the home or food service operation, BUT it can be found as an infection of dairy cows. It has been reported that 2% of raw milk world-wide contains Listeria and that 16% of dairy cows are infected. Although usually inactivated by pasteurization, large microbial loads can make pasteurization ineffective. Listeria bacteria can be isolated from cows with mastitis, manure, soil, and in poorly fermented, moldy silage. Besides mastitis, it can cause abortions, circling disease, and death in animals. Mastitis usually occurs as chronic subclinical cases with occasional clinical flare-ups. New mastitis infections can be spread through dirty udders and teats, milkers' hands, and milking equipment. Attention should be paid to cleanliness of cows and loafing/exercise areas and use of clean and dry towels for cleaning teats before milking. These recommendations are important in prevention of any kind of mastitis. Silage should be properly preserved so that it will undergo desired fermentation. This includes dry matter content, rapid filling of tower silos and packing of horizontal silos to minimize air entrapment, and length of chop. Be sure to feed enough off the top or face to prevent spoilage. Pathogenic (disease-causing) microorganisms are ranked by scientific experts as the number 1 potential risk to public health, with 3-14% of the U.S. population becoming ill every year due to bacterial contamination of food somewhere between farm and table.

L monocytogenes is a harmful and disease causing bacterium. And even though it is less common than E. coli, Listeria is more deadly (2). What is remarkable about this organism is its resistance to harsh environments. It can survive the effects of freezing, drying, and heat, all of this and without the formation of spores (1). It can be isolated from soil and other environmental sources, but is clinically defined when isolated from blood, cerebrospinal fluid or, as in the case of pregnant women, taken from the placenta of the fetus (1). Under most circumstances, Listeria is killed by pasteurization, and heating procedures used to prepare ready-to-eat processed meats should be sufficient to kill the bacterium (3). But sometimes if poor manufacturing practices occur so can the contamination of such foods after the processing stage.

Anyone can get this disease but those who are at the highest risk are new babies, the elderly, people with weakened immune symptoms such as those with AIDS, cancer, diabetes, patients who have received transplants, and those patients who are taking steroid medications (2). But probably the highest risks come to pregnant women. Many pregnant women find out too late that they have been infected with Listeria. This is a sad scenario that is all too real. For example, the other night I was watching a popular news program that featured a story about a young woman who went into premature labor after eating some cold hot dogs. She was in the 6th month of her pregnancy, and sadly, she lost her baby due to the hot dogs she ate a couple of days before. Infection of the fetus can occur before delivery and thus may cause a spontaneous abortion as early as in the first trimester of pregnancy but all to often it can happen in the 3rd trimester. In fact, pregnant women are so much at risk for getting Listeriosis; they account for 1/3 of all cases reported (4). And pregnant women are about 20 times more likely to become infected with Listeria than the average healthy adult (4).

Signs and symptoms associated with Listeriosis usually occur within a month of exposure, but they can start to appear as soon as a couple of days after exposure. Listeria can be more harmful than other bacteria in that it can cross contaminate from the GI tract into the blood stream and from there into other tissues and organs of the body (2). This is why some cases of Listeriosis can cause mild symptoms such as a stomachache and vomiting, while other severe cases could lead to meningitis. When meningitis occurs from Listeria, the overall mortality rate can be as high as 70%; and from the sepsis 50% can be infected; 80% are infections from the perinatal and neonatal population. Usually, a person with Listeriosis develops symptoms such as fever, muscle aches, nausea or diarrhea. If the infection spreads to the nervous system, symptoms like headache, stiff neck, confusion, dizziness, or convulsions can occur (2). It is not known how much of a dose of L. monocytogenes is needed to cause Listeriosis, but it safe to say that less than a total of 1,000 organisms may cause disease (1). And as mentioned before, the infected pregnant woman can develop mild symptoms that can lead to deadly outcomes. The U.S. Food and Drug Administration is urging pregnant women to eat only hard cheeses instead of soft cheeses during their pregnancy. Some Mexican-style soft cheeses are very popular in the Hispanic population, and these can easily become contaminated with Listeria (5).

Treatment of the Listeria infection includes antibiotic therapy like Ampicillin, either alone or in combination with other antibiotics. And when the pregnant woman becomes infected prompt use of antibiotics must be administered in order to prevent disease to the fetus. If a baby becomes infected he too can use the same antibiotics as used in an adult for treatment. But most often, the baby dies due to an immature immune system. There are general guidelines that are recommended for the prevention of Listeriosis and other foodborne pathogens (3), these include:

-Cooking foods thoroughly, especially those from animal sources such as beef, pork, or poultry.

-Wash vegetables thoroughly before consumption.

- Do not use the same plate used the prepare the uncooked meats, and keep separate from ready-to-eat foods.

- Avoid raw or unpasteurized milk or those foods that were made from raw milk.

…-And most importantly, practice good hand washing techniques when handling uncooked foods.

On the Federal level, the FDA is currently examining how to prevent the contamination of potentially hazardous foods by ensuring sufficient temperatures while food is being transported and distributed (6).

As of the moment, studies show that the common temperature of transported foods is around 41şF. But as noted early, Listeria can survive, and in some cases even multiple at temperatures as low 25şF. So laws must be changed to warrant the safety of foods. Also, Government agencies and other food industries have taken steps to reduce contamination of food by Listeria. Through proper monitoring, a processed food is looked at more closely now that Listeria has been identified. Sometimes when foods slip through the cracks the tarnished food must be recalled, as in the recent case of the Lowell Packing Company. The company is recalling approximately 4,500 pounds of hot dogs and smoked sausages that are possibly contaminated with the Listeria microbe (7).

There is a great risk for Listeriosis; here in the United States, around 1,100 persons become seriously ill with Listeria each year and of these, 250 die (4). Another source lists the number of cases reported are 1,600 per year with a total of 415 deaths per year (1). Since the majority of these cases are sporadic, it is difficult to make any connection in the epidemiology, although tests are being studied in current outbreaks of this pathogen. One outbreak was reported in California in 1985, that was linked to Mexican-style soft cheese that led to a number of stillbirths (1). Another outbreak took place in Philadelphia, PA in 1987; this outbreak involved specific food links that were only made epidemiological in this cluster. And recently, in New York, 16 deaths involving Listeria might have been caused by dust from nearby construction at a Sara Lee's meat processing plant (2). This outbreak was traced to hot dogs and deli meats processed at this plant. Officials have already recalled the products by the Bil Mar Foods division of Sara Lee.

Listeriosis is a serious infection caused by eating contaminated food that contains the aerobic and facultative anaerobic gram-positive bacillus _L. monocytogenes_. It is commonly found in soil, water, fertilizer, vegetation, human and animal feces, and processed food. In addition, the organism is carried in the intestinal tract of numerous mammals, birds, fish, and shellfish. As a result, sporadic and common-source outbreaks of listeriosis can be easily traced to meat and dairy products.(4,5)

Can listeriosis be treated? When infection occurs during pregnancy, antibiotics given promptly to the pregnant woman can often prevent infection of the fetus or newborn. Babies with listeriosis receive the same antibiotics as adults, although a combination of antibiotics is often used until physicians are certain of the diagnosis. Even with prompt treatment, some infections result in death. This is particularly likely in the elderly and in persons with other serious medical problems. e, b, b, c, f. What is being done? Government agencies and the food industry have taken steps to reduce contamination of food by the Listeria bacterium. The Food and Drug Administration and the U. S. Department of Agriculture monitor food regularly. When a processed food is found to be contaminated, food monitoring and plant inspection are intensified, and if necessary, the implicated food is recalled. The National Center for Infectious Diseases (NCID) is studying listeriosis in several states to help measure the impact of prevention activities and recognize trends in disease occurrence. NCID also assists local health departments in investigating outbreaks. Early detection and reporting of outbreaks of listeriosis to local and state health departments can help identify sources of infection and prevent more cases of the disease.

_L. monocytogenes_ has a unique means of transmission and growth. The bacterium is initially phagocytosed into epithelial cells and hepatocytes where it becomes encased in a phagolysosome. This acidic environment activates the exotoxin, listeriolysin-O, which lyses the organelle membrane and releases its contents into the host cell's cytoplasm. Here the bacteria proliferate, migrate to the cell membrane to form elongated protrusions, and are subsequently ingested by adjacent cells where the mechanism repeats itself. Listeria, therefore, spreads from cell to cell without contacting the extracellular environment, hence the immune system's immunoglobulins and complement do not play an active role in defense of the pathogen.(4) Its presence in phagocytic cells permits access to the brain and most likely transplacental passage to the fetus in pregnant women. The pathogenesis of _L. monocytogenes_ is based on its remarkable ability to survive and replicate in phagocytic host cells. An hypothesis currently being researched, proposes the host cell's contractile system, specifically its cytoskeletal protein actin aids in the cell-to-cell transmission which ultimately causes listeriosis.

Listeria can cause many clinical afflictions, most notably, septicemia (death rate ~ 50%), meningitis (death rate ~ 70%), endocarditis, pneumonia, and perinatal/neonatal infections (death rate ~ 80%). Listeriosis starts with flu-like symptoms such as persistent fever, muscle aches, chills, and sometimes gastrointestinal ailments. If the infection further involves the central nervous system, a headache, a stiff neck, confusion, loss of balance, or convulsions can occur. Of particular interest, the most prominent sign of the disease in cattle gives listeriosis its nickname, "Circling Disease," whereby infected cattle are often seen walking in circles. More subtle signs in cows include uncoordinated movements, leaning against objects, and progressive paralysis. In humans, a direct invasion of the cerebral cortex and brain stem is possible, causing a syndrome called rhomboencephalitis. Another illness, meningoencephalitis, is usually associated with numerous cranial nerve deficits, especially the VIth and VIIth nerves. As previously mentioned, Listeria's ability to cross the meninges and blood-brain barrier is likely due to macrophage or endothelial cell phagocytosis and contractile system domination. Closely related to Listeria's intracellular nature, the bacteria are seldom visible in gram stains of cerebrospinal fluid which adds to the conflicting results available to diagnostic clinicians.

Listeria's unusual intracellular lifestyle may explain the higher incidence of listeriosis in persons already at increased risk such as pregnant women, newborns, the elderly, and immunocompromised patients. Its infective dose is unknown but is thought to depend on the specific bacterial strain as well as the susceptibility of its host. Clinically, the disease can be positively diagnosed when the organism is cultured from blood, cerebrospinal fluid, stool, or an otherwise normally sterile sites (fetus, placenta, etc.).

Thus far, successful treatment of the disease involves treatment with the antibiotics ampicillin and penicillin. From a non-medical standpoint, general recommendations for reducing the risk of the disease are good, standard household and cooking techniques. For instance, raw food from animal sources should be cooked well and raw vegetables should be washed thoroughly. Uncooked meats should be kept separate from vegetables, cooked foods, and ready-to-eat foods. And unpasteurized milk or foods made from raw milk should be avoided. Above all, diligent attention should be paid to carefully washing hands and cooking utensils. For those groups at higher risk, extra precautions are needed to adequately heat leftovers or ready-to-eat foods and to avoid soft cheeses or food items from deli counters.

In the past, outbreaks occurred in California (1985), in which ingestion of Mexican-style cheese caused numerous stillbirths. Based on this episode, the U.S. Food & Drug Administration increased its monitoring and removal of suspect imported cheeses. In an outbreak in Pennsylvania (1987), a specific food link was made epidemiologically. Recently, the Centers for Disease Control positively established a connection between raw hot dogs and undercooked chicken.

Listeria is a type of bacteria people are hearing more and more in the news due to recalls of millions of pounds of meat. However, Listeria are found almost everywhere in the environment, including water and soil. There have been outbreaks of food poisoning from Listeria in milk, cheese, ice cream, meat, chicken, alfalfa sprouts, salad bars, and many other foods.

Listeria is not usually harmful to most people. Pregnant women and those with less than perfect immune systems (especially the very young and elderly) are more susceptible to infection. Miscarriages can result from these bacteria, and they have one of the highest mortality rates (about 22% of all infections result in death, compared with less than 1% for Salmonella).

HERE'S WHAT YOU NEED TO KNOW: Listeria is a problem because the usual methods of preservation, including refrigeration, only slow its growth. Meats and dairy products have been the major foods involved in recalls because these products provide all the nutrients and moisture bacteria need for rapid growth. Proper food handling and thorough cooking of foods is essential to reduce your chances of a nasty encounter with this bug.

Listeria is a type of bacteria which is widespread in the environment and has been found in water, soil and raw foods such as poultry and certain types of cheeses. The department of health confirm that the disease caused, by this bacteria, listeriosis, is rare, but the numbers of cases are increasing. However, only a handful of cases have been directly attributed to eating contaminated food. Listeria is a potential hazard in chilled food as unlike other food poisoning bacteria such as salmonella, it can survive and grow at refrigeration temperatures as low as 5°C (41°F).

Research at King's College and Queen Charlotte's hospitals has shown that pregnant women are susceptible to listeria infection and risk passing it on to their unborn baby. It is believed that a significant number of miscarriages and stillbirths may be caused by listeria infection and recent research suggests that listeria infection is the third most common cause of septicaemia (blood poisoning) and meningitis in the new-born.

The two related studies demonstrate that consuming contaminated foods is a major cause of listeriosis, a rare bacterial disease that chiefly affects pregnant women and their fetuses and people with weakened immune systems; it poses minimal risk to most healthy individuals. The CDC studies estimate that the disease causes some 1,850 illnesses and 425 deaths annually in the United States. The projection is based on 301 confirmed cases of listeriosis identified by CDC researchers in four California counties, four Tennessee counties, eight Georgia counties and the state of Oklahoma during the period from Nov. 1988 through Dec. 1990. Some 18 million persons live in the study area. Preliminary CDC data for 1991 suggest a decrease of 30 to 40 percent in the number of listeriosis cases in the four states compared to those in 1989 and 1990. FSIS, a part of the U. S. Department of Agriculture which oversees meat and poultry products, and FDA, which regulates most other foods, routinely monitor and test foods for potential Listeria contamination. Testing was begun as a result of several outbreaks during the 1980s. Both FDA and FSIS take regulatory action -- recalls, detentions or seizures -- against products found to contain any detectable levels of Listeria monocytogenes, the organism that causes the listeriosis disease. The following can be used to answer public inquiries: Listeria monocytogenes is one of a related group of Listeria bacteria that are found throughout the environment -- in water, soil, silage and dust -- and on a wide variety of foods. k, b, i, j, a. It is the only Listeria organism linked to human disease. The CDC study associates illness with consumption of Mexican style cheeses and feta cheese, delicatessen and other ready-to-eat foods, and undercooked chicken.

What you can do: All dairy products are important sources of calcium which is needed for the healthy growth and development of your baby. However, cheeses such as Brie, Camembert, Dolcelata and goat's cheeses should be avoided. Hard cheeses e.g. Cheddar, Cheshire, processed and cottage cheeses, yoghurt and pasteurised milk can be taken and will make a valuable contribution to your calcium intake.

"Ready to eat" cook chilled foods purchased from supermarkets such as cooked poultry and prepared packaged salads, especially those which are cabbage based, should be avoided. It is also important to avoid foods which are outside their "best before" or "eat within" date.

Cooking foods thoroughly will destroy listeria and make the food safe to eat. If you use a microwave, be sure to follow cooking instructions carefully; standing times are very important as they allow time for heat to penetrate evenly to all parts of the food. it is advisable to purchase a microwave thermometer to ensure temperatures exceed 90°C (194°F) in all parts of the food.

When purchasing chilled foods, buy them at the end of your shopping trip and bring them straight home and put them quickly into your refrigerator. It is important to make sure your fridge is working properly and keep the food at temperatures less than 5°C (41°F) by checking with a fridge thermometer.

Listeria Monocytogenes is a gram positive faculative intracellular pathogen. It causes severe infection of both humans and animals resulting in such conditions as listeriosis, meningoencephalitis, abortion, and septicemia. While such infections are fairly rare, they are quite serious and can have very high mortality rates. Most commonly affected are immunocomprimised individuals and pregnant females but healthy individuals can also be infected. Outbreaks of listeriosis can be found in domestic ruminants as the result of ill-prepared silage, a fermented vegetable fodder.

The method of entry into the host is primarily through the digestive system and, hence, contaminated food. This pathogen manages to cross through the normally protective intestinal barrier by causing non-phagocytic epithelial cells to phagocytose. L. monocytogenes then lyse the phagosomal membrane and replicates in the eukaryotic cytoplasm. During replication the polymerization of host-cell actin on the surface of the pathogen is initiated. This actin will eventually form a propulsive tail on one end of the bacterial cell and allow the bacteria to reach the surface of the host cell where it extrudes a pseudopod-like structure. The pseudopodium is then taken up by a nearby cell and the bacteria repeats the process of lysing the vacuole and replicating in the new cell.

As these bacteria must be able to survive in a free environment as well as that of a host they are capable of living in varying conditions including temperatures ranging from 3°C to 45°C, pH from 4.5 to 9, and osmolarities up to 10% NaCl. In order to prevent the waste of energy and maximize its chances of survival, L.monocytogenes must only express their virulence genes when they enter a host. It is believed that virulence is therefore mediated by a group of factors that indicate in some way a drastic change in environment.

The majority of the regulation of virulence in L. monocytogenes is thought to occur through the 273 base pair product of prfA, PrfA. PrfA is named as an acronym for positive regulation factor. The genes shown thus far to be regulated by PrfA include plcA, hlyA, the genes of the lecithinase operon, and five other unknown genes. The regulation of these genes by PrfA is supported by complementation tests in which non-haemolytic mutants were restored through the presence of wild type PrfA. inlA and inlB are partly regulated by PrfA but they are also thermoregulated. The method of regulation consists of PrfA binding to what have been named "PrfA boxes" by many scientists. These boxes consist of conserved 14 base pair sequences with dyad, or palindromic, symmetry centered around -41. Evidence has been given that PrfA-regulated genes are differentially regulated - hlyA and plcA are better transcribed than mpl and actA - and that this is most likely due to how close their PrfA-boxes are to being perfectly symmetrical. One experiment by Renzoni et al (source 5) actually demonstrated that more symmetrical boxes gave genes with higher expression. PrfA has also been suggested to be capable of repression of the same genes it activates through cooperative binding of several PrfA molecules. This is thought to be why the expression of genes under its control decreases late in the stationary phase of L. monocytogenes and also suggests a mechanism by which PrfA could downregulate its own synthesis.

The transcription of prfA itself is rather involved as it has three promoters and it is thought that its activity may be partly controlled through varying the ratios of the transcripts formed from the different promoters. Two of the promoters are found within plcA, located directly upstream from prfA, and produce a monocistronic transcript. The third is found before plcA and supplies a positive regulation loop for PrfA as this promoter is PrfA dependant. Therefore, when PrfA is present, this promoter is activated to give a bicistronic transcript consisting of plcA-prfA. plcA was originally thought to be transcriptionally independent as it has a promoter back to back with hlyA's promoter and a putative terminator 17 base pairs after its stop codon. Experimental results, however, showed that prfA and plcA are cotranscribed at the beginning of exponential growth and that plcA's terminator does not act as a transcription stop signal under all circumstances. Bicistronic transcription has actually been shown to give better activation of virulence genes, possibly because prfA's two monocistronic promoters are weaker than the biscistronic one.

Sugars, or carbon sources, are thought to regulate virulence through a combination of several different mechanisms such as changes in pH, effects on growth rate, and specific regulatory proteins. There are also several different mechanisms for each of the factors. For example, there is much evidence to indicate that the presence of ß-glucoside cellubiose strongly represses hly and plcA (part of PrfA regulon) but the same experiment shows that the levels of PrfA protein are not affected. This would seem to indicate that this regulation is completely unrelated to PrfA as these two genes are linked and may involve interaction with common promoter region. The repression of by cellubiose, however, indicates that regulation by ß-glucosides must interfere with PrfA while another possibility is that this regulation is part of global catabolite regulation. Similar results came from experiments using arbutin, another ß-glucoside. As cellubiose and arbutin are unique to plants they are probably abundant in decaying plant matter. L. monocytogenes uses decaying vegetation for its primary growth substrate so these and other ß-glucosides may act as "specific signature molecules" that allow the bacteria to sense it is in soil.

This suggestion was refuted by Milenbachs et al (source 4) as strains of L. monocytogenes exist that show repression by other readily metabolized sugars such as glucose and fructose. This group also demonstrated that repression only occurred for any of these carbohydrates when enough of the carbohydrate was present to significantly stimulate growth. This lent more support to a general or global CR mechanism. However, the same group showed that using a homolog of transcription factor CcpA in this bacteria did not affect carbon source regulation. The remaining possibilities are that other CR mediators and pathways exist and that there may be two sugar-sensing pathways. The idea of two sugar-sensing pathways results from the fact that a particular mutant known as NCTC 7973 is only regulated by cellubiose. Other studies have indicated a link between virulence and the regulation of utilizable carbon sources. The utilization of carbohydrate glucose-1-phosphate is coordinately regulated with other virulence factors and is dependent on PrfA, the major activator of virulence genes.

Ultimately, it was decided that there is a virulence repression pathway for ß-glucosides independent of the CR mechanism that is presumably used by glucose and other common utilizable sugars. It has been suggested that this pathway may have various sugar-sensing mechanisms, each with different substrate specificities. This would explain the varying responses to the different ß-glucosides. As well, it should be noted that all PrfA-regulated genes are repressed by this pathway. The possibility of yet other mechanisms exists.

Further research on repression by ß-glucosides: The bvr locus has been determined to be specifically involved in ß-glucoside-mediated repression and bvrABC compose the operon. Again, it has been confirmed that the CR pathway is not involved. One possible mechanism is that BvrB dephosphorylates and activates BvrA upon transport of cellubiose and salicin. This would give positive regulation, by transcriptional antitermination, of a putative effector system responsible for the inhibition of the PrfA regulon. Another possibility is that BvrC is involved in posttranscriptionally controlling PrfA function. The bvr locus is not, however, thought to be required for transport as it can be mutated without affecting the ability of the bacteria to use ß-glucosides. Other transport systems must therefore exist and the bvr locus must be redundant as far as transport is concerned. Its main function is more likely to determine the environment in which the bacterium finds itself.

There is a decrease in pH associated with utilization of sugars that can cause down regulation of virulence genes but sugars can affect virulence even when pH is kept constant. It is therefore thought that there may be pH-dependent and pH-independent components. The following figure from Behari and Youngman for paper shows experimental data of the effect of pH on virulence expression.

pH-dependent regulation is not due to general down regulation as growth and the basal level of activity of alpha-glucosidase are not affected. It must therefore be a specific regulatory effect. pH-dependent regulation may be caused by altering PrfA activity, either by changing PrfA levels or the activity of a putative PrfA-associated factor Starvation has also been known to upregulate virulence along with pH. This is thought to be due to the fact that both these conditions would be found inside phagosomes of activated macrophages

Temperature:
Virulence genes are expressed above 37°C, but not below 26°C (or 20°C depending on what source is consulted) May involve : detection of change from free environment to animal host the PrfA-dependent promoter of plcA-prfA which seems to be important in thermoregulation (see PrfA regulation) An increase in temperature is not enough for full activation of the PrfA regulon; at least one other environmental factor is required for full expression of virulence Composition of the Growth Medium: Regulation of this sort is suggested by the fact that there is little or no virulence at 37°C with a rich medium like BHI, but the addition of absorbent activated charcoal or substitution with minimal essential medium causes induction. - chemical parts of environment must therefore also be important in PrfA regulation L. monocytogenes is thought to be able to detect iron levels in its growth medium -as iron levels are generally low in extracellular host compartments this would cause induction of virulence

The outbreak of a deadly bacteria from Bil Mar Foods' products has raised concerns that federal regulators are doing a poor job of controlling food-borne illnesses. And U.S. Department of Agriculture officials admit they may no longer have control of listeria.

The 16 deaths and 72 illnesses caused by contaminated hot dogs and lunch meats from the Borculo meat processing plant has placed scrutiny on current methods for testing and inspecting ready-to-eat foods.

About one-third of the 301 identified cases were linked to these foods. "Mexican style" cheeses in the study are soft, white, ethnic Hispanic/Latin American cheeses -- for example, Queso Blanco, Queso Fresco, Queso de Hoja, Queso de Puna, Queso de Crema and Asadero. Past studies have implicated such cheeses as Brie, Camembert and blue-veined cheeses such as Roquefort. Whether a person becomes ill from Listeria depends greatly on an individual's health. Exposure to foods with Listeria does not automatically mean one will get ill. For most healthy people, a moderate dose of Listeria bacteria on an ingested food is not likely to cause illness. The scientific community is still uncertain how many Listeria organisms it takes to cause illness; an infective dose varies with an individual's susceptibility. Exposure to high levels can make a healthy person ill, although such cases are extremely rare. Listeria primarily affect pregnant women, or, more correctly, the fetus; newborn infants; the elderly; people with cancer or AIDS and others whose immune systems have been weakened by serious illness; people whose immune system is suppressed either by medications, such as corticosteroids, or by chemotherapy treatment; and patients suffering from liver disease and diabetes. d, g, k, e, f. Listeria infection during pregnancy can lead to spontaneous abortions or stillbirths or to serious illness in a newborn child. Prompt treatment with antibiotics is often necessary for those who are seriously ill, though such treatment is not always effective. (See FSIS-FDA Backgrounder for details on symptoms and onset of disease.) Although the number of people infected each year is small compared to other, better known causes of foodborne illness, listeriosis is nevertheless a concern to public health authorities.

"We are very concerned because the current best practices anyone knows for preventing listeria contamination don't seem to be good enough anymore," said Margaret Glavin, associate administrator for the USDA's Food Safety and Inspection Service.

USDA officials, who have been criticized for waiting too long before asking Bil Mar to recall products they suspected were contaminated, will begin to re-evaluate the process for controlling listeria, Glavin told reporters during a media teleconference Thursday.

The USDA began in 1989 to test for listeria in ready-to-eat products, those that do not require cooking to be eaten. The program reduced illnesses by 44 percent and deaths by 48 percent over the next four years, but the numbers did not continue to drop.

"We're looking at what changes are needed in the protocol to control listeria and to continue to drive those numbers down," Glavin said.

During 1998, the USDA tested 3,500 product samples from roughly 2,000 plants making ready-to-eat products. About 2.5 percent tested positive for listeria. USDA officials have not committed to stepping up the random testing.

They have come up with several ideas for the increase in listeria cases, such as the bacteria may have become more heat resistant, or maybe longer product shelf lives are causing problems. But they still have no answers.

The USDA is holding a public meeting Wednesday to discuss how to reduce listeria illnesses and is working with the Food and Drug Administration on a risk assessment program for the bacteria, Glavin said. Since the Bil Mar incident, Oscar Mayer and Thorn Apple Valley have also recalled products due to possible listeria contamination.

Sara Lee, Bil Mar's parent company, voluntarily recalled 15 million pounds of hot dogs and packaged meats on Dec. 22. But the federal Centers for Disease Control and Prevention had been investigating the listeria outbreak since August.

The CDC has a nationwide information bank that tracks food-borne illnesses, which is where the listeria cases first turned up, Glavin said. CDC investigators began following the illness reports and taking food histories of the patients. They determined the patients had something in common -- hot dogs. That's when they contacted the USDA, which regulates meat processing plants.

Although USDA inspectors first entered the Bil Mar plant Dec. 15, it wasn't until Dec. 30 that the CDC found listeria in an unopened package of Bil Mar hot dogs. Random sampling of products by the USDA had not turned up any listeria.

Glavin said CDC and USDA officials met with Sara Lee representatives on Dec. 18 and "urged a market withdrawal" of products, but did not have enough evidence to formally request a recall.

"At that time, there was still epidemiological evidence only," Glavin said. "At that time, there was not pure evidence that Bil Mar products were contaminated."

The time lapse between the USDA getting involved and Bil Mar issuing the recall have prompted some to say federal inspectors failed to act quickly enough.

"That's absolutely not the case," Glavin said. "We were following this very closely to determine whether there was in fact a link that would cause us to request a recall."

Bil Mar has yet to pinpoint the cause of the listeria, according to Bill Smith, assistant deputy administrator of USDA field operations. That's why the plant must evaluate every inch of its operation, from employee practices to equipment and facilities.

Bil Mar laid off 241 employees Tuesday to begin a year-long restructuring of the plant, which is to include state-of-the-art food safety technology. Sara Lee officials said Wednesday the plant plans to resume production of some deli meats by the end of the month.

Some production has continued since the recall, but Smith said those products are either raw and require cooking, or are processed in a bag and never exposed to the environment.

Bil Mar can only return to production if it can show USDA inspectors that the plant's environment and products are safe, Smith said.

Even though federal regulators say standard methods for controlling listeria are not working, they have not discouraged consumers from purchasing ready-to-eat products.

"We have not moved in the direction of that kind of recommendation," said Glavin. She pointed out that listeria is not a threat to healthy adults, though it can affect the elderly, pregnant women, children and people with weak immune systems.

And while cooking products will kill the bacteria, that doesn't solve the problem of lunch meat.

Food science is biology, physics, social studies and engineering all put together with the goal of making safer food. Food scientists are microbiologists and chemists that make food safe from harmful bacteria and chemicals. The engineers are the ones that develop safer processes to produce food. -Why do we care about Listeria? We care about Listeria monocytogenes because is a food borne pathogen that is the most deadly organism currently recognize in the US, causing approximately 10% of all deaths associated with food borne illnesses. As Listeria monocytogenes is commonly isolated as a free-living bacterium from diverse locations, including food-processing environments, this organism presents a daunting public health challenge in that it is extraordinarily difficult to ensure its absence from the US food supply. As a common and potentially deadly food contaminant, and as a organism for which good genetic tools already exists, Listeria monocytogenes presents an excellent model system for exploration of genetics determinants that affect the ability of a food borne pathogen to cause disease. We propose using Lysteria monocytogenes as a model for probing the roles of bacterial general stress response system that are mediated by alternative sigma factors in the pathogenesis of food borne and gastrointestinal disease. What is sigma-B? Sigma-B is a small protein; that is part of RNA polymerase. It is also required to start RNA transcription by RNA polymerase. Without the RNA, you can’t make protein- i.e. cell loses function. Sigma-B is stress related, that means that it helps the cell to pass through stress related situations like exposure of cells to heat, acid, ethanol, salt stress or starvation for glucose or oxygen. If we regulate sigma-B in any organism there is no way that it could possibly survive those kinds of conditions.

We are assuming that Listeria monocytogenes has a protein, RsbP that is involved with sigma-B regulation. What are we trying to do is find out if there is a RsbP protein is Listeria monocyotogenes. We are using the RsbP sequence from Bacillus subtilis, to design PCR primers and use on Listeria monocytogenes. We are doing that to see if RsbP regulates sigma-b activity, which controls stress responses in Listeria. We want a better understanding of how sigma-B is activated, so we can control stress-responses and possibly virulence.

Federal investigators suspect dust kicked up during a summer maintenance project at Sara Lee Corp.'s Bil Mar Foods plant in Borculo may have been the source of a listeriosis outbreak that has killed 15 and sickened about 75 people in 16 states.

Investigators with both the U.S. Department of Agriculture and the federal Centers for Disease Control and Prevention are looking into whether work conducted on an air-conditioning system at the Bil Mar Foods meat-processing plant in Borculo was responsible for spreading the bacteria Listeria monocytogenese into hot dogs and other packaged meat products.

Maintenance on the air-conditioning system performed in one of the rooms at the plant July 4, "could have caused widespread contamination of meat products throughout the plant," according to a USDA memorandum dated Dec. 22. The USDA found a dramatic increase in the amount of Listeria levels after July 4.

The first listeriosis case traced back to Bil Mar Foods occurred on Aug. 2. It has since killed 12 adults and caused three miscarriages.

Paul Mead, a medical epidemiologist who is leading the investigation of the listeriosis outbreak for the CDC, said there are several theories into how Listeria infected Bil Mar meats but the link to work on the air-conditioning system was "the leading hypothesis." CDC investigators suspect the construction work generated dust that settled on equipment in the plant, which then contaminated products as they rolled over the equipment.

Sara Lee spokeswoman Theresa Herlevsen said the company hasn't yet determined the exact source of contamination. She said it's "possible" that work on the air-conditioning system spread the bacteria, but added "there are lots of possible sources for Listeria."

Indeed, Listeria bacteria is found in soil, water and various raw foods and can easily settle into the tiniest nooks of meat-processing equipment. It can cause listeriosis and result in death. Pregnant women, the elderly, newborns and adults with weakened immune systems are most susceptible to it. In healthy people, listeriosis may cause short-term flu-like symptoms.

Since Sara Lee announced the recall of certain hot dogs and deli meats on Dec. 22, the company has been cleaning up the Bil Mar Foods plant and brought in a team of outside quality-assurance experts.

Bil Mar Foods has also instituted new rules at the plant to cut down on the risk of spreading bacteria, according to some Bil Mar Foods employees.

For now, federal investigators are focusing on the theory that "substantial construction" performed on a ceiling-fixed air-conditioning system sparked the outbreak.

On the hot dog production line, three of 12 samples taken from May 26 to July 4 tested positive for Listeria. But 27 of 34 samples taken from July 5 to Nov. 5 were positive, according to the document.

Still, nagging questions remain about the viability of this explanation, the USDA investigator admits in the memo. For one, the tests identify only the presence of Listeria in general and not the specific pathogen and subtype linked to the listeriosis outbreak. Another problem is it's unlikely Listeria could have been spread through the plant's ventilation systems.

CDC estimates that about one-fourth of the cases are fatal -- a much higher fatality rate than for other common foodborne diseases. In addition, the population potentially at risk is growing as a result of improved treatment for patients with cancer and kidney failure, the rising number of persons with AIDS, and the expanding elderly population. FDA and FSIS both play an active role in protecting consumers against foodborne diseases such as listeriosis. FDA monitors soft cheeses and other dairy products, and processed seafood products, and FSIS monitors processed meat and poultry products. State and local agencies are responsible for overseeing food handling practices of retail food establishments, such as restaurants, delis and supermarkets. The two federal agencies have provided the retail sector with educational materials that stress the importance of proper food handling, food sanitation, refrigeration and cooking procedures. Leftovers or ready-to-eat foods such as hot dogs should be heated until steaming hot before eating. j, g, i, k, d. In addition, the agencies have prepared brochures and other educational materials for consumers and special population groups such as pregnant women, immunocompromised persons and health professionals. Public health experts at CDC, FDA and FSIS offer the following advice to the general public for reducing risk: -- Thoroughly cook all foods of animal origin.

L.monocytogenes is now known to be "widely distributed in nature"(6). It can be found in soil, silage,fodder, and water. It has also been isolated from at least 37 domestic and feral mammalian species, at least 17 species of bird, some fish, crustaceans, and ticks. According to several studies 2 to 6% of the healthy population are human carriers of L.monocytogenes in their intestinal tract. Since the incidence of L.monocytogenes found in food is higher than reported cases, some experts believe that ingestion of low levels of the bacterium does not constitute a serious health risk(2,10).

However, amongst the vulnerable population, L.monocytogenes is a life threatening problem. Those most at risk are: pregnant women, newborns, the immunocompromised, and the elderly. Pregnant women contribute 30% of all cases and are 20 times more likely to contract Listeriosis than a normal healthy individual(9).

The fetus can contract Listeriosis in utero or during passage through the birth canal. Even though the mother may be asymptomatic or show influenza-like symptoms (fever, myalgia, and headache) the newborn may experience respiratory distress, refusing to drink, vomiting. Extreme symptoms include neonatal septicimia (blood poisoning) or meningitis. 40% of all Listeriosis cases occur in newborns. Infection to the mother may also lead to spontaneous abortion (2nd/3rd trimester) or stillbirth. Transmission can also be by direct contact with infectious material (soil, contaminated feces, and aborted animal fetuses). These symptoms can include papular lesions on the hands and arms. Eating food contaminated with L.monocytogenes may result in influenza-like symptoms, gastrointestinal symptoms (diarrhea, nausea, and vomiting), encephalitis, meningitis, maningeoencephalitis, organ infections, endocarditis and septicemia. If permanent neurologic damage occurs this can lead to mental retardation, blindness, hearing loss, and seizures (9,10).

L.monocytogenes is characterized as a gram positive, non-sporulating, bacillus that has temperature dependent motility and is an opportunistic facultative intracellular bacterium. 7 serotypes have been identified, but 3 serotypes (1/2a, 1/2b, and 4b) are responsible for 95% of Listeriosis cases. Between 1981-1993 serotype 4b was responsible for foodborne outbreaks in North American and Europe(2).

Pathogenesity occurs when the bacterium attaches and invades the intestinal mucosa. It enters the lamina propia and may be phagocytosed by a phagocyte. L. monocytogenes produces the toxin listeriolysin O (LLO) that ruptures the phagosome, enters the cytoplasm of the cell where it multiplies. In order to move itself from one cell to another is uses directional actin assembly. As soon as the bacteria enter a host's monocytes, macrophages, or leukocytes, it is able to travel in the blood and invade other tissues, even the brain and possibly transplacental migration to the fetus. It's pathogenic character relies on its ability to survive and multiply in host cells. Incubation could take up to six weeks and makes investigating Listeria outbreaks difficult (6,7).

Human diagnosis is made by cultivating the bacterium from the cerebrospinal fluid, blood (anti-listerolysin O serology test), placental, or fetal tissue, genital tract secretions, amniotic fluid or a specimen from an otherwise normally sterile site(5). The Food and Drug Administration (FDA) method for food diagnosis requires 24-48 hours of enrichment and the total time for identification could take up to 7 days. Laboratory indications of Listeria monocytogenes include: catalase +, motility at room temperature, growth at 4 degress Celsius, and beta-hemolysis. Selective plating is suggested for: modified McBride, LPM agar, Listeria selective medium (Modified Oxford formulation), and PALCAM. New DNA recombinant technology could take up to 3 days for analysis.

The incidence of Listeriosis is 0.5 per 100,000 population. In the United States approximately 1,100 people become seriously ill with Listeriosis each year and about 250 die. L.monocytogenes has the highest case fatality rate of 20 percent(2).

In order to prevent Listeriosis, it's recommended that meats be cooked to a uniform internal temperature of 121 degress Celsius. Cold foods should be kept at or below freezing, since L.monocytogenes can grow 4 degrees Celsius. Observe and follow all "keep refrigerated", "Sell by", and "use by" dates on processed foods. Avoid "raw" or unpasteurized dairy items. Perpare fruits and vegetables and ready-to-eat foods separate from uncooked meats, and always wash raw vegetables and fruits before eating(4,8).

Those populations more at risk (pregnant women, the elderly, and immunocompromised) may wish to be avoid soft cheeses (Brie, Camembert, Mexican-style, and feta) and heat left-overs and ready-to-eat foods until they are steaming. Listeria monocytogenes is killed during pasteurization and heating procedures used in ready-to-eat processing meat plants, but unless good manufacturing practices are followed, contaminated can occur after processing.

L.monocytogenes is sensitive to disinfectants and antibiotics such as: penicillin, ampicillin, aminoglycosides, tetracyclines, and chloramphenicol.

The contact of T cells to cross-reactive antigenic determinants expressed by nonpathogenic environmental micro-organisms may contribute to the induction or maintenance of T cell memory. This hypothesis was evaluated in the model of murine Listeria monocytogenes infection. The influence of nonpathogenic L. innocua on the L. monocytogenes p60-specific T cell response was analyzed. We show that some CD4 T cell clones raised against purified p60 from L. monocytogenes cross-react with p60 purified from L. innocua. The L. monocytogenes p60-specific CD4 T cell clone 1A recognized the corresponding L. innocua p60 peptide QAAKPAPAPSTN, which differs only in the first amino acid residue. In vitro experiments revealed that after L. monocytogenes infection of APCs, MHC class I-restricted presentation of p60 occurs, while MHC class II-restricted p60 presentation is inhibited. L. innocua-infected cells presented p60 more weakly but equally well in the context of both MHC class I and MHC class II. In contrast to these in vitro experiments the infection of mice with L. monocytogenes induced a strong p60-specific CD4 and CD8 T cell response, while L. innocua infection failed to induce p60-specific T cells. L. innocua booster infection, however, expanded p60-specific memory T cells induced by previous L. monocytogenes infection. In conclusion, these findings suggest that infection with a frequently occurring environmental bacterium such as L. innocua, which is nonpathogenic and not adapted to intracellular replication, can contribute to the maintenance of memory T cells specific for a related intracellular pathogen.

Drugs used in the chemotherapy of cancer have also been used as immunosuppressive agents for the control of immune mechanisms involving antibody production, and cell-mediated forms of immunity such as delayed type hypersensitivity and transplantation immunity (1-5); there are, however, few published reports of their effect on the immune response to microorganisms despite infection being a serious complications of their use in clinical practice. The present report deals with the influence of some immunosuppressive drugs on the immune response to a facultative intracellular parasite.

Cooking kills the organism. Raw meat should be cooked or reheated to an internal temperature of 160 degrees Fahrenheit, poultry to 180 degrees and raw fish to 160 degrees or until it is white and flaky. -- Keep hot foods above 145 degrees. To prevent any Listeria present from multiplying, do not leave foods out at room temperature for more than two hours. -- Wash raw vegetables thoroughly before eating. Few illnesses have been linked to such products. The advice is precautionary. -- Separate uncooked foods such as meat, poultry and vegetables from cooked and ready-to-eat foods and keep the refrigerator clean to prevent cross-contamination. -- Avoid raw (unpasteurized) milk or foods made from raw milk. Pasteurized dairy products pose little known risk unless mishandled after pasteurization. -- Follow common sense sanitation procedures by washing hands, knives and cutting boards after handling uncooked foods. -- Follow label instructions with products that must be refrigerated and which have a "use by" date. For those at high risk, this additional advice is offered: -- Avoid soft cheeses (such as Mexican style soft cheeses, feta, Brie, Camembert and blue-veined cheeses such as Roquefort). f, e, h, a, e. Hard cheeses, processed slices, cottage cheese, cream cheese and yogurt do not present a problem. Although the risk of listeriosis associated with foods from delicatessen counters is relatively low, pregnant women and immunosuppressed persons may choose to avoid these foods and to thoroughly reheat cold cuts before eating.

Tuberculosis, brucellosis, listeriosis, and salmonellosis are examples of infections which give rise to a cell-mediated form of immunity which evolves through similar mechanisms (6); it is therefore logical to assume that observations on one host-parasite system will have relevance to the others. Listeriosis in the mouse has been chosen as a model for the present study because it offers several advantages. Firstly, the immune response sets in early and runs a short course, so that an immunosuppressive effect is quickly revealed; secondly, a Listeria infection, as assessed by bacterial enumeration, provides an accurate and quantitative assessment of immunity and the magnitude of the immunosuppressive effect obtained with drugs. Mice infected with a sublethal dose of Listeria monocytogenes develop an immune response which interrupts the growth of the organisms in vivo. The experiments to be described are based upon the premise the effective suppression of the immune response by drugs would result in continued multiplication of Listeria, particularly in the spleen and liver.

Listeria monocytogenes, Shigella flexneri, and Rickettsia conorii are three bacterial pathogens that are able to polymerize actin into 'comet tail' structures and move within the cytosol of infected cells. The actin-based motilities of L. monocytogenes and S. flexneri are known to require the bacterial proteins ActA and IcsA, respectively, and several mammalian cytoskeleton proteins including the Arp2/3 complex and VASP (vasodilator-stimulated phosphoprotein) for L. monocytogenes and vinculin and N-WASP (the neural Wiskott-Aldrich syndrome protein) for S. flexneri. In contrast, little is known about the motility of R. conorii. In the present study, we have analysed the actin-based motility of this bacterium in comparison to that of L. monocytogenes and S. flexneri. Rickettsia moved at least three times more slowly than Listeria and Shigella in both infected cells and Xenopus laevis egg extracts. Decoration of actin with the S1 subfragment of myosin in infected cells showed that the comet tails of Rickettsia have a structure strikingly different from those of L. monocytogenes or S. flexneri. In Listeria and Shigella tails, actin filaments form a branching network while Rickettsia tails display longer and not cross-linked actin filaments. Immunofluorescence studies revealed that the two host proteins, VASP and (alpha)-actinin colocalized with actin in the tails of Rickettsia but neither the Arp2/3 complex which we detected in the Shigella actin tails, nor N-WASP, were detected in Rickettsia actin tails. Taken together, these results suggest that R. conorii may use a different mechanism of actin polymerization.

Thermal inactivation of Listeria innocua and 6 Salmonella serotypes in ground chicken breast meat was compared to that in peptone (0.1%) - agar (0.1%) solution. Inoculated samples were packed in a thin-wall metal tube and submerged in a water bath at temperatures ranging from 55.0 to 70.0 °C. For Salmonella and Listeria, the D values in ground chicken breast meat at 55 to 70 şC were higher (p < 0.0001) than those in peptone-agar solution; however, the z values were not significantly different. Complete first-order inactivation models, with Arrhenius temperature dependency, were developed for each inoculum and medium.

Listeria monocytogenes is found commonly in wild animals, domesticated animals, and in people who have close association with domestic animals such as slaughterhouse workers and dairy farmers. Listeriosis is a common cause of spontaneous abortion and stillbirth in domestic animals. L. monocytogenes also occurs as a food-borne contaminant that can cause disease in humans particularly pregnant women.

In humans, Listeriosis most often causes a generalized blood infection (septicemia) or meningitis (inflammation of the covering of the brain). The foetus, newborn, and pregnant women are particularly susceptible. The immunocompromised people such as those being treated for cancer, those with organ transplants, and those with AIDS are at increased risk.

Infection of a pregnant woman early in pregnancy generally leads to spontaneous abortion. The organism may be transmitted across the placenta. Infections in late pregnancy may lead to stillbirth or an infant who dies within a few hours of birth. About half of infants infected at or near term will die.

Listeria refers to a genus (related group) of bacteria. One species in this genus, Listeria monocytogenes, can cause a serious bacterial infection called listeriosis. Usually when public health officials refer to Listeria, they are referring specifically to Listeria monocytogenes.

Where is it Found?

Researchers to have isolated L. monocytogenes from soil, leaf litter, sewage, silage, dust and water. The organism often moves through the animal and human intestinal tract without causing illness, and has been found in many domestic and wild animals, including birds and fish. Because L. monocytogenes is widely present in the environment, it would be impossible to prevent animals from coming in contact with the bacteria. However, farmers, animal producers, food processors and food handlers can all take steps to reduce contamination and keep food safe from L. monocytogenes.

Is it New?

L. monocytogenes is not "new." Since 1911, scientists have known it infects animals, and in 1929 the first case of human infection was detected. What is new is the recognition that L. monocytogenes bacteria may be spread in food. In earlier time, many believed farm animals transmitted L. monocytogenes to farm workers. But when listeriosis appeared in city dwellers, public health authorities realized that animal contact was not always the source of disease transmission.

It has been only in the past decade that researchers have recognized L. monocytogenes as an agent of foodborne illness. Fecal contamination is one way the organism is spread to raw agricultural products. For example, farm animals may pick it up from consuming improperly fermented silage, and then vegetables may become contaminated when animal manure carrying the organism is used for fertilizer. Animals in a herd also may pick up L. monocytogenes from other animals or manure containing the organism.

Is it Unusual?

L. monocytogenes is a remarkable tough organism. It resists heat, salt, nitrite and acidity much better than many organisms. The bacteria survive on cold surfaces and also can multiply slowly at 24 degrees Fahrenheit, defeating one traditional food safety defense--refrigeration. (Refrigeration at 40 degrees Fahrenheit or below stops the multiplication of many other foodborne bacteria. Refrigeration does not kill most bacteria.) Commercial freezer temperatures of 0 degrees fahrenheit, however, will stop L. monocytogenes from multiplying. Discrepancies in information available on proper cooking prompted FSIS in 1988 to contract with a private laboratory to conduct research that has become the basis for FSIS regulations on proper cooking of roast beef. Earlier work focused on cooking temperatures and times needed to destroy Salmonella. The new study conducted by the laboratory looked at cooking temperatures and times that will destroy L. monocytogenes, and confirmed the adequacy of current regulatory cooking standards for eliminating the organism in FSIS-regulated products.

In addition, FDA researchers and FDA-funded research have confirmed the adequacy of commercial pasteurization for eliminating the organism in dairy products.

Post-processing contamination, rather than failure of heating or pasteurizing processes, is usually suspected when L. monocytogenes is detected on processed products.

How is it Detected in Food?

Once L. monocytogenes were identified as foodborne bacteria that could cause serious illness, scientists began looking at methodology used to detect the bacteria. FSIS scientists developed a more precise method for detection in meat and poultry products. FDA scientists developed a similar method appropriate for dairy products, seafood and vegetables. These methods have steadily improved over the years. FDA and FSIS developed culture procedures that rely on the presence of antibiotics in the medium, which allow multiplication of L. monocytogenes but inhibit multiplication of competing organisms. In 1986, independent laboratories verified the accuracy of the new FSIS method for meat and poultry. The FDA method has also been reviewed and accepted.

As more is learned about the bacteria and their control, new and even better tests are being developed. An example is FDA's gene- probe method.

THE ILLNESS

How is it Transmitted?

Listeriosis is the disease caused by the bacteria L. monocytogenes. Consumers most commonly contract listeriosis by eating food contaminated with the organisms. (See section on ) Also, the scientific literature contains a few isolated reports of occupational listeriosis; for example, farm workers and veterinarians who work with animals have developed minor skin infections..

Who is Most at Risk?

Healthy people do not often develop noticeable listeriosis symptoms after eating food containing L. monocytogenes. However, some people are very susceptible to the disease. The highest incidence of listeriosis has been in persons over 60 years old and newborns. One third of infections occur during pregnancy and may lead to spontaneous abortions or serious illness in newborns. Others most at risk include patients with immune systems compromised by cancer, AIDS, or immunosuppressive medications such as steroids; and patients suffering from cirrhosis, diabetes and ulcerative colitis.

What are the Symptoms?

The disease symptoms are variable and depend on the individual's susceptibility. Symptoms may be limited to fever, fatigue, nausea, vomiting and diarrhea. However, these symptoms can precede a more serious illness. The more serious forms of listeriosis can result in meningitis (brain infections) and septicemia (bacteria in the bloodstream). Pregnant women may contract flu-like symptoms of listeriosis; complications can result in miscarriage, stillbirth, or septicemia or meningitis in the newborn. In older children and adults, complications usually involve the central nervous system and blood stream, but may include pneumonia and endocarditis (inflammation of the lining of the heart and valves). Skin contact with L. monocytogenes can cause localized abscesses or skin lesions.

It takes from one to six weeks for a serious case of listeriosis to develop, although flu-like symptoms may occur 12 hours after eating L. monocytogenes-contaminated food. Onset time probably depends on the health of the patient, the strain of L. monocytogenes and the dose--or amount of bacteria-- ingested.

Outbreaks

Four reported outbreaks of listeriosis in North America in the past decade are either known or suspected to have been caused by L. monocytogenes in food.

An outbreak in 1981 in Nova Scotia resulted in 41 cases of listeriosis including 18 deaths; 83 percent of the cases were perinatal (occurring near the time of birth). The outbreak was traced to L. monocytogenes on coleslaw that had been made from cabbage grown in field fertilized with manure from Listeria-infected sheep.

An outbreak in 1983 in Boston resulted in 49 cases of listeriosis including 14 deaths; 14 percent of the cases were perinatal, the remainder in immunocompromised adults. Although pasteurized milk from Listeria-infected dairy cows was linked to the outbreak, L. monocytogenes was not found in the suspected brand of milk.

An outbreak in 1985 in Los Angeles resulted in 142 cases of listeriosis including 46 deaths; 85 percent of the cases were perinatal. The outbreak was traced to L. monocytogenes on soft, Mexican-style cheese, manufactured with contaminated milk.

An outbreak in Philadelphia in 1987 resulted in at least 32 cases of listeriosis, including 11 deaths. The cause was never identified.

. . .And Other Cases Linked To Food

The Food and Drug Administration funded a Centers for Disease Control (CDC) active surveillance project in 1986. CDC began contacting all acute care hospitals and their respective laboratories in an area that included five states and Los Angeles county. From the 1986-1987 study results, as well as from findings in studies conducted form 1989-1990, CDC determined that sporadic (non-outbreak) individual cases of listeriosis were associated with soft cheese, undercooked poultry, hot dogs not thoroughly reheated and food purchased from delicatessen counters.

How Much Can You Eat Before Getting Sick?

Researchers are not sure how many L. monocytogenes organisms it takes to cause illness. The infective "dose" varies, depending on the susceptibility of the individual. (See "Who is most at risk?") However, it is noteworthy that four of the ill persons in the Los Angeles outbreak reported eating the implicated product (highly contaminated soft cheese) only once. Thorough cooking will destroy L. monocytogenes on foods. Nonetheless, FDA and FSIS are committed to reducing contamination of raw foods by L. monocytogenes and other potentially harmful bacteria.

What is the Incidence?

From information gathered in its surveillance projects conducted in the 1980's, CDC projects about 1,850 cases of human listeriosis occur annually. Incidence, however, varies from state to state. CDC is now encouraging state health departments to conduct surveillance programs for listeriosis so that outbreaks may be rapidly identified and investigated. As our population ages and more people live longer with malignancies and other immunosuppressive illnesses, many experts believe the number of people at risk for listeriosis is likely to increase. Surveillance data also indicate that about 425 deaths occur each year in the United States. The probability of death varies greatly depending on the patient's age and status of immune function. (See section on "Who is most at risk?") About 5 percent of the 9,000 food poisoning deaths each year are due to listeriosis.

Preliminary data suggest that the rate of listeriosis may have declined substantially during 1991 in several areas, perhaps related to intensified efforts to reduce Listeria contamination of foods.

How is Listeriosis Diagnosed and Treated?

Listeriosis can be positively diagnosed, using clinical laboratory techniques, only by culturing the organism from blood or cerebrospinal fluid. Listeriosis can be treated with antibiotic drugs such as penicillin or ampicillin.

CONTROLLING LISTERIA IN THE PLANT

FSIS and FDA have identified the Hazard Analysis and Critical Control Point (HACCP) system as the most effective strategy for controlling the presence of L. monocytogenes and other pathogenic bacteria on food products. In addition to encouraging adoption of this strategy by all who handle food, from farm worker to plant processor to consumer, the agencies are working with industry to design strong HACCP programs. Most of the food industry supports HACCP. In a HACCP, points at which food risks are more likely to be introduced are identified, and interventions are introduced where control is possible to reduce the potential for consumption of unsafe products. For instance, insufficient cooking or raw meat, poultry or milk may allow the survival of pathogenic bacteria and present a hazard. Therefore, the agencies require adequate cooking temperatures to destroy the bacteria.

Areas of concern in food processing plants include plant design and layout, equipment design, process control, personnel practices, cleaning and sanitizing procedures, and verification of pathogen control.

Much of the dairy industry has already instituted control measures, based on HACCP principles. Other FDA-regulated industries are following the lead. In 1987, meat companies began to modify production facilities, such as rearranging plant layout and making changes in equipment. An industry working group also developed recommendations for all meat companies based on what is learned, and developed a training video on employee practices and plant hygiene. The poultry industry also instituted improvements.

The food industry, FSIS and FDA have conducted workshops to develop recommendations for controlling risks at critical points. Government and industry, including food processors and grocers, are also working with retail establishments and hotels and other institutions to identify critical control points and interventions to address hazards.

FOOD HANDLER CONTROL

Listeria bacteria do not change the taste or smell of a food. As a final check, food handlers--in homes, restaurants and institutional kitchens--must follow basic food safety procedures for destroying any potentially harmful bacteria, thereby avoiding any foodborne illness. The Centers for Disease Control, FDA, FSIS and the National Advisory Committee on Microbiological Criteria for Foods (which includes food scientists from federal health agencies, universities and private industry) have developed food handler advice for preventing listeriosis.

Recommendations for all Individuals Although most people are at very low risk for listeriosis, the risk of listeriosis and other foodborne illnesses can be reduced by following these tips:

Avoid raw/unpasteurized milk.

Keep raw and cooked foods separate when shopping, preparing, cooking and storing foods. Otherwise, bacteria in juices from raw meat, poultry or fish might contaminate a cooked food. For instance, transfer cooked meat, poultry or fish to a clean platter -- never to the dish that held the raw food of animal origin.

Wash hands, knives, and cutting boards after handling uncooked foods.

Wash raw vegetables thoroughly before eating.

Thoroughly cook all food of animal origin, including eggs. Cook raw meat to an internal temperature of 160 degrees Fahrenheit, raw poultry to 180 degrees Fahrenheit, and raw fish to 160 degrees Fahrenheit or until it is white and flaky. Reheat leftovers thoroughly.

Read and follow label instructions to "keep refrigerated" and "use by" a certain date.

Keep hot foods to (above 140 degrees Fahrenheit). Do not keep them out for longer than two hours at room temperature - at which L. monocytogenes can thrive - before eating.

Keep cold foods cold (at or below 40 degrees Fahrenheit). Do not keep them out for longer than two hours at room temperature before eating.

Divide leftovers into small, shallow covered containers before refrigerating, so that they chill rapidly and evenly.

Keep your refrigerator clean and keep the temperature at 34-40 degrees Fahrenheit.

Recommendations to High-Risk Individuals Persons at increased risk for listeriosis such as pregnant women, the elderly, and those with immunosuppressive conditions can decrease the risk by:

Avoiding soft cheese such as Mexican style, feta, Brie, Camembert and blue cheese. Mexican-style cheeses are soft, white, ethnic (Hispanic-Latin American) cheeses such as Queso Blanco and Queso Fresco. There is no need to avoid hard cheese, processed slices, cottage cheese or yogurt.

Reheating leftover foods or ready-to-eat foods such as hot dogs thoroughly until steaming hot before eating.

Although the risk of listeriosis associated with foods from delicatessen counters is relatively low, pregnant women and immunosuppressed persons may choose to avoid these foods or to thoroughly reheat cold cuts before eating.

What Is Listeriosis?

Listeriosis or Listeria infection is an illness that may result from eating food contaminated with bacteria known as Listeria monocytogenes. The infection may cause few or no symptoms in healthy people, but can cause serious illness in people who are particularly- at risk including:

pregnant women and their babies the newborn the elderly; and those whose immune systems have been weakened by disease or drugs, for example cancer or transplant patients.

What Are the Symptoms?

Healthy people, including pregnant women may show no symptoms. In others, symptoms vary from minor complaints such as fever, headache, tiredness, aches and pains, vomiting and diarrhoea to more serious forms of the illness such as meningitis (brain infection) and septicaemia (blood poisoning). Less common symptoms are diarrhoea, nausea and abdominal cramps.

In a pregnant woman, Listeria is usually a mild illness. A high temperature before or during labor may be the only sign. The fetus can be seriously affected leading to miscarriage, stillbirth, premature birth or a very ill newborn. The death rate in babies and fetuses affected has ranged from thirty to fifty percent. Infection of the fetus usually occurs about three days after the mother's infection.

Symptoms of Listeriosis can appear from one to ninety days after eating the contaminated food, making it difficult to establish an association with a particular food.

How Common Is Listeriosis?

Listeriosis is a relatively uncommon disease. Since the disease was made notifiable in Victoria in 1990, the number of cases notified has ranged from thirteen to twenty-four a year. These have all been isolated. Sporadic case outbreaks of Listeriosis however have been reported in Europe and North America over the past ten years, and in 1990 an outbreak affecting pregnant women was reported in Western Australia. In the outbreaks, soft cheese, milk, raw vegetables and paté were implicated.

Can Listeriosis Be Treated ?

Listeriosis can be successfully treated with antibiotics (that are safe for unborn fetuses) if commenced early.

Where Is Listeria Found?

Listeria monocytogenes is widespread and commonly found in soil, vegetation and sewage. It has also been found in a variety of foods ranging from raw meat, raw vegetables and unpasteurised milk to processed foods such as soft cheese, paté, diced chicken, sliced deli meat, and smoked fish and smoked mussels. The bacteria can be transmitted to man through contamination of food. Listerias are unusual in that they can grow and multiply in food under refrigeration temperature. They are, however, readily killed by adequate heating.

How Can Listeria Infection Be Avoided?

As Listeria is commonly found in the environment, it is impossible to eradicate it and some exposure to the bacteria is unavoidable, though most people are at low risk for listeriosis. Avoiding cross-contamination of food through good food hygiene and proper food handling can however, reduce the risk for listeriosis. At risk people can further reduce the risk of listeriosis by taking special dietary precautions. Listeria infection can also cause illness and abortion in farm animals. Pregnant women should therefore avoid contact with the afterbirth and aborted animal fetuses on a farm or in veterinary clinics.

Listeriosis is a disease caused by a bacterium, Listeria monocytogenes, commonly called "Listeria." People most often get listeriosis by eating foods that are contaminated with Listeria. In nature, Listeria is commonly found in soil and water. Listeriosis in healthy adults has flu-like symptoms such as fever and chills. Occasionally, an upset stomach will develop. People at risk--young, elderly, or those with weakened immune systems--may develop symptoms such as headache, stiff neck, confusion, loss of balance, or convulsions. Symptoms usually occur within 72 hours, although it may take up to 8 weeks for someone to become ill.

Listeria is an organism that is able to reproduce at refrigeration temperatures. This can be significant in certain ready-to-eat products that have a long shelf life and require refrigeration.

How does Listeria get into my food? Animals can be carriers of the bacteria even though they show no clincal symptoms of the disease. Listeria bacteria live in the intestines, which makes the contamination of meat and dairy products possible. The best way to keep Listeria out of food is by killing it in a cooking process or by other heating methods such as pasteurization. The Listeria problem often is associated with ready-to-eat foods contaminated after processing in a manufacturing plant.

Ready-to-eat foods of concern include hot dogs, luncheon meats, cold cuts, fermented or dry sausage, and other deli-style meat and poultry. Outbreaks have also been connected to unpasteurized dairy products.

Who is most likely to develop listeriosis? Listeriosis is a disease that may cause few or no symptoms in healthy people. Those at high risk to develop listeriosis include pregnant women, newborns, elderly, and people with weakened immune systems caused by cancer treatments, AIDS, diabetes, and kidney disease. People in this high risk group may become seriously ill if they eat foods that contain Listeria. Pregnant women may experience very mild symptoms, but the mother's illness can be transmitted to the fetus through the placenta. This can lead to miscarriage, stillbirth, or serious health problems for the newborn child.

If you are at risk and/or have symptoms that concern you, consult your health care provider. Listeriosis is successfully treated with antibiotics.

What can I do to prevent listeriosis? Consumers who are in the high risk group should follow these food safety practices to prevent listeriosis and other foodborne illnesses: * Reheat ready-to-eat foods until they are steaming hot. This includes hot dogs, luncheon meats, cold cuts, fermented and dry sausage, and other deli-style meat and poultry product. If you do not reheat them, do not eat them.

* Consume only pasteurized milk and dairy products made from pasteurized milk.

* Do not eat soft cheeses such as feta, Brie, Camembert or blue-veined varieties.

All consumers are reminded to follow the following food safety practices to reduce their risk of foodborne illness:

* Clean. Wash hands, surfaces, utensils, cutting boards, and dishes with hot, soapy water. Listeria can grow slowly at refrigeration temperatures; therefore, use hot, soapy water to clean up spills in the refrigerator.

* Cook. Cook foods to safe temperatures. Contact your county Extension office for USDA recommended cooking temperatures.

* Chill. Refrigerate or freeze perishables, including ready-to-eat foods and leftovers. Do not leave these foods in the temperature danger zone (40 to 140 degrees F) for more than 2 hours. Keep refrigeration temperatures at 35 to 40 degrees F. Leftovers should be used within 1 to 3 days and reheated to a safe temperature of 165 degrees F.

* Separate. Don't cross-contaminate. Ready-to-eat foods and raw meat, poultry, and sea-food can contain dangerous bacteria. Keep these foods separate from vegetables, fruits, breads, and other foods already prepared for eating.

* If you have a food item that is recalled by the federal government or processor because of Listeria or other bacterial contamination, do not eat it. Return the recalled food to the place where you purchased it.

Listeriosis is a dangerous, food-borne bacteria that can cause serious illness in a fetus, including meningitis and pneumonia. It can even result in a miscarriage. Unlike most bacterial invaders, it bypasses the protective amniotic membrane and infects fetuses through the mother's bloodstream.

Listeriosis finds an ideal home in unpasteurized, soft cheeses such as brie, mozzarella and blue cheese. It also lurks in soil and is present on some raw vegetables. The bacteria aren't new, but Johns Hopkins obstetrician Dr. Frank Witter notes that listeriosis is more widespread than ever before.

"Now, with wide transportation of food products all over the country, there's a possibility for having more people affected by a contamination at one site," says Dr. Witter.

The good news: listeriosis is easy to avoid. Watch the cheeses, and thoroughly cook food. Experts also advise skipping foods that have been left out at room temperature for more than a couple of hours.

In France, listeriosis surveillance is based on two complementary sytems: the routine molecular typing of isolates sent to the National Reference Center which allows early identification of clusters and the mandatory notification of all clinical cases with the routine collection of food history. In January 2000 a small nationwide outbreak of listeriosis involving 10 cases received extensive media attention when the incriminated product "rillettes" was withdrawn from the market. In the aftermath of the recall, a second nationwide outbreak of listeriosis occurred caused by a Listeria strain different from the strain of the first outbreak.

Methods

To identify risk factors for infection we carried out a case control study. A case was defined as a patient, resident in France, from whom the outbreak strain was isolated from a usually sterile site, between November 1, 1999 and March 1, 2000. Controls were sporadic cases of listeriosis infected with a strain other than the strains involved in the present and previous outbreak, diagnosed in France from December 1, 1999 to March 1, 2000. At the moment of their illness, all cases and controls had been asked about underlying medical conditions and consumption of 74 specific foods in the 2 months prior to their illness, as part of the routine enhanced surveillance of listeriosis.

Results

A total of 32 cases were identified in 26 departments, between November 12, 1999 to February 28, 2000. Overall 14/29 (48 %) cases and 1/32 (3%) controls reported eating pork tongue in jelly. After controlling for consumption of other meat products, patients infected with the outbreak strain were more likely to have consumed pork tongue in jelly (OR 75.5; 95% CI 4.7 - 1216.0) and farmers pâté (OR 8.9; 95% CI 1.7 - 46.1). Based on the results of the epidemiological investigation, the health authorities advised not to consume any pork tongue in jelly. Trace back results did not allow to incriminate a single manufacturer of pork tongue in jelly, nor of farmers pâté, among the suppliers of the retail outlets of the cases. The outbreak strain has not been isolated from the incriminated foods, nor from any production sites.

Conclusions

This was the second outbreak in France linked to the consumption of pork tongue in jelly. As in the previous outbreak, pork tongue in jelly did not account for all cases and it is likely that other meat products such as pâté, cross-contaminated either at the delicatessen counter in retail outlets or at the production site, were also involved as vehicles of transmission. The consecutive occurrence of two outbreaks underlines the importance of ongoing case surveillance and systematic typing of the strains allowing to investigate the two events separately.

Listeria monocytogenes is the pathogenic species of the genus Listeria. Pathogenesis extends to both humans and animals, causing the fatal disease listeriosis. In sheep, the disease is associated with silage feeding and in particular with silage of the big bale type. This research project has two main aims: firstly, to obtain a measure of risk of contaminated silage using the techniques of systems modelling and risk analysis and secondly to develop models that describe the growth of listeria in big bale silage under typical outdoor storage conditions. This work is undertaken in collaboration with Moredun Research Institute, Scottish Agricultural Statistics Service and Scottish Veterinary Investigation Services.

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