Chapter 132. Infections Caused by Listeria monocytogenes (Part 2)

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Immune Response The innate and acquired immune responses to L. monocytogenes have been studied extensively in mice. Shortly after IV injection, most bacteria are found in Kupffer cells in the liver, with some organisms in splenic macrophages. Listeriae that survive the bactericidal activity of initially infected macrophages grow in the cytosol and spread from cell to cell. In the liver, the result is infection of hepatocytes. Neutrophils are crucial to host defense during the first 24 h of infection, while influx of activated macrophages from the bone marrow is critical subsequently. Mice that survive sublethal infection clear the infection within...

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Nội dung Text: Chapter 132. Infections Caused by Listeria monocytogenes (Part 2)

Chapter 132. Infections Caused by Listeria monocytogenes (Part 2) Immune Response The innate and acquired immune responses to L. monocytogenes have been studied extensively in mice. Shortly after IV injection, most bacteria are found in Kupffer cells in the liver, with some organisms in splenic macrophages. Listeriae that survive the bactericidal activity of initially infected macrophages grow in the cytosol and spread from cell to cell. In the liver, the result is infection of hepatocytes. Neutrophils are crucial to host defense during the first 24 h of infection, while influx of activated macrophages from the bone marrow is critical subsequently. Mice that survive sublethal infection clear the infection within a week, with consequent sterile immunity. Knockout mice have been used to show that interferon γand tumor necrosis factor (TNF) are essential in controlling infection. While innate immunity is sufficient to control infection, the acquired
immune response is required for sterile immunity. Immunity is cell-mediated; antibody plays no measurable role. The critical effector cells are cytotoxic (CD8+) T cells that recognize and lyse infected cells. The bacteria grow and spread from cell to cell. The host recognizes and lyses infected cells, and extracellular bacteria are killed by circulating activated phagocytes. A hallmark of the L. monocytogenes model is that killed vaccines do not provide protective immunity. The explanation for this fundamental observation is multifactorial, involving the generation of appropriate cytokines and the compartmentalization of bacterial proteins for antigen processing and presentation. Epidemiology L. monocytogenes usually enters the body via the gastrointestinal tract in foods. Listeriosis is most often sporadic, although outbreaks do occur. Recent annual incidences in the United States range from 2 to 9 cases per 1 million population. No epidemiologic or clinical evidence supports human-to-human transmission (other than vertical transmission from mother to fetus) or waterborne infection. In line with its survival and multiplication at refrigeration temperatures, L. monocytogenes is commonly found in processed and unprocessed foods of animal and plant origin, especially soft cheeses, delicatessen meats, hot dogs, milk, and cold salads. Because food supplies are increasingly centralized and normal hosts tolerate the organism well, outbreaks may not be immediately apparent; pulsed-field gel electrophoresis has proved useful in linking cases to
specific foods. FoodNet, an active U.S. surveillance program, has demonstrated decreases in listeriosis incidence, although recent data from some European countries show a stable or increased number of cases, perhaps because of enhanced active surveillance. The U.S. Food and Drug Administration has a zero- tolerance policy for L. monocytogenes in ready-to-eat foods. Diagnosis Symptoms of listerial infection overlap greatly with those of other infectious diseases. Timely diagnosis requires that the illness be considered in groups at risk: pregnant women; elderly persons; neonates; individuals immunocompromised by organ transplants, cancer, or treatment with TNF antagonists or glucocorticoids; and patients with a variety of chronic medical conditions, including alcoholism, diabetes, renal disease, rheumatologic illness, and iron overload. Meningitis in older adults (especially with parenchymal brain involvement or subcortical brain abscess) or a local outbreak of culture-negative febrile gastroenteritis should trigger consideration of L. monocytogenes infection. Listeriosis occasionally affects healthy, young, nonpregnant individuals. HIV- infected patients are at risk; however, listeriosis seems to be prevented by trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis targeting other AIDS- related infections. The diagnosis is typically made by culture of blood, cerebrospinal fluid (CSF), or amniotic fluid. L. monocytogenes may be confused with "diphtheroids" or pneumococci in gram-stained CSF or may be gram-variable
and confused with Haemophilus spp. Serologic tests and polymerase chain reaction assays are not clinically useful diagnostic tools at present. Clinical Manifestations Listerial infections present as several clinical syndromes, of which meningitis and septicemia are most common. Monocytosis is seen in infected rabbits but is not a hallmark of human infection. Gastroenteritis Appreciated only since the outbreaks of the late 1980s, listerial gastroenteritis typically develops within 48 h of ingestion of a large inoculum of bacteria in contaminated foods such as milk, deli meats, and salads. Attack rates are high (50–100%). L. monocytogenes is neither sought nor found in routine fecal cultures, but its involvement should be considered in outbreaks when cultures for other likely pathogens are negative. Manifestations include fever, diarrhea, headache, and constitutional symptoms. The largest reported outbreak occurred in an Italian school system and included 1566 individuals; ~20% of patients were hospitalized, but only one person had a positive blood culture. Isolated gastrointestinal illness does not require antibiotic treatment. Surveillance studies show that 0.1–5% of healthy asymptomatic adults may have stool cultures positive for the organism.
Bacteremia L. monocytogenes septicemia presents with fever, chills, and myalgias/arthralgias and cannot be differentiated from septicemia involving other organisms. Meningeal symptoms, focal neurologic findings, or mental status changes may suggest the diagnosis. Bacteremia is documented in 70–90% of cancer patients with listeriosis. A nonspecific flulike illness with fever is a common presentation in pregnant women. Endocarditis of prosthetic and native valves is an uncommon complication, with reported fatality rates of 35–50% in case series. A lumbar puncture is often prudent, although not necessary, in pregnant women without central nervous system (CNS) symptoms.