Listeriosis: causes, symptoms, diagnosis, treatment, prognosis, and prevention

Listeriosis is an acute infectious disease caused by Listeria monocytogenes, mostly in the neonates, old adults, pregnant women, and patients with immunodeficiency.


Causes

Listeria monocytogenes is widely distributed in nature. It is known that 42 kinds of mammal such as sheep and cattle and 22 kinds of bird can be infected, and the bacteria can be isolated from fishes, ticks, flies, and crustaceans. The bacteria can infect various animals and are a common cause of encephalitis and abortion of ruminants. 1% - 5% of normal persons and 10% - 20% of slaughterhouse workers are asymptomatic carriers, and the bacteria evacuated from the digestive tract contaminate the soil, water, and environment. The bacteria are mainly transmitted through foods such as cheese, milk, ice cream, raw steak, lamb chops, and lettuces, and can enter the human body through the mouth, eyes, and wounded skin and mucous membranes. Listeriosis is mostly sporadic, more common in late summer and early autumn. Susceptible persons are newborns, pregnant women, and adults over 40 years old. Sex differences in morbidity are absent.

Listeria monocytogenes is a facultative anaerobic, non-pore-forming, motile, flagellated, Gram-positive bacillus, grows in a variety of culture media, and is resistant to alkali but nonresistant to acid. The optimum culture temperature is 35 - 37 °C, and the bacteria grow poorly below 4 °C. The bacteria can ferment a variety of carbohydrates, and can produce acid but not gas. Positive catalase, methyl red, and Voges-Proskauer (VP) reaction are present. Mucopolysaccharide capsules can be formed in serum-containing glucose peptone water. Zones of hemolysis can be produced on the blood agar plates. The bacteria are arranged in pairs in the cerebrospinal fluid specimens, resembling cocci, and can be mistaken for pneumococci. The bacteria over decolorized in Gram stain resemble influenza bacillus, sometimes very confusing with diphtherold baclus.

Pathogenesis

After entering the gastrointestinal tract, the bacteria are taken in by the endocytosis of epithelial cells of the small intestine microvilli, infecting macrophages, disseminating to the whole body with the macrophages. Listeria monocytogenes can produce hemolysin, which binds to cholesterol in the cytomembrane, causing death of macrophages. Similar to mycobacterium tuberculosis and Salmonella, the pathogen is an intracellular parasite that can reproduce in monocytes and macrophages. Various factors, such as iron compounds, catalase, superoxide dismutase, bacterial surface components, and hemolysin, can affect the growth and pathogenicity of Listeria monocytogenes in cells. The elimination of the bacteria relies mainly on cellular immunity.

Pregnant women present very mild symptoms after infection, but if the bacteria are transmitted to the fetus or neonate through the placenta or birth canal, serious infection is often present. Fetal pathological examination reveals that disseminated, multiple, pinhead sized, yellowish white abscesses are prominently in the liver, followed by spleen, adrenal gland, lung, gastrointestinal tract, and central nervous system. Focal necrosis and massive neutrophil and monocyte infiltration are visible in microscopy. Gram-positive bacilli can be found in the necrotic area. The autopsy of patients with meningitis reveals suppurative leptomeningitis and ependymitis, often accompanied by splenomegaly, focal necrosis, and inflammation of the liver, adrenal gland, and lung.


Signs and Symptoms

The incubation period ranges from few days to several weeks. The most common clinical listeriosis is meningitis, followed by bacteremia, lesions of central nervous system with or without meningitis, and endocarditis, merely uveitis, endophthalmitis, cervical lymphadenitis, pneumonia, empyema, myocarditis, peritonitis, hepatitis, liver abscess, cholecystitis, osteomyelitis, and arthritis.

Meningitis

Meningitis is more common in newborns, adults with low immunity, patients with diabetes or liver cirrhosis, and patients who are being treated with glucocorticoid steroids. 30% of patients do not have obvious incentives. Sudden onset, severe headache, vertigo, nausea, fever, and neck stiffness are present in most patients, and some patients have convulsions, irritability, and disorientation. The symptoms are similar to those of other meningitis caused by pyogenic bacteria, and coma can occur 24 - 48 hours after onset in severe patients. Slow onset, a long duration, and repeated recurrences are present in few patients. About 1/4 of patients have focal nerve lesions. If cerebral parenchyma is involved, encephalitis, rhombencephalitis, and brain abscess may occur. Convulsions, hemiparesis, epileptic seizure, and herniation can be present. Some patients have only low fever and personality changes. Prodromal symptoms such as 3 - 10 days of fever, headache, and vomiting are followed by asymmetrical dysfunction of cranial nerve V, VI, VII, VIII, IX, and X. In addition, ataxia, paresis, and dysesthesia may occur. Most patients without meningitis have normal results of cerebral spinal fluid tests, or are only with mild lymphocytosis and increased protein contents. Positive blood cultures are present in most patients with lesions in the central nervous system.

Septicemia

Septicemia can be found in the immunosuppressed adults and newborns. The clinical manifestations are similar to those of other Gram-negative septicemia, but the count of large mononuclear cells can be as high as 8% or more in leukocytes, if the patient has no lymphoma, which has diagnostic value. Positive blood culture can help confirm the diagnosis.

Neonatal listeriosis

Neonatal listeriosis is infected through the placenta. Multiple abscesses or granuloma or both occur in multiple internal organs such as liver, spleen, lung, kidney, and brain. Amniotic fluids are contaminated by the meconium. Patients are weak and often accompanied by conjunctivitis, pharyngitis, and red papules mostly on the trunk and extremities. Respiratory and circulatory failures may occur, and a high mortality rate is present.

Listeriosis in pregnancy

Pregnant women with listeriosis account for 1/3 of all patients. Patients present with chills, fever, sore throat, myalgia, dorsalgia, spasmodic colic, and diarrhea. The signs and symptoms are not special and generally do not affect the fetus. Severe infection can cause miscarriage, stillbirth, premature birth, or neonatal infection.

Focal infection

Focal infection can be caused by local contact or hematogenous dissemination. Infective endocarditis caused by Listeria monocytogenes does not occur in patients with low immune function, but is associated with lesions of left heart. 2/3 of patients are with aortic valve disease, and 1/3 of patients are with tricuspid valve disease. New or altered heart murmurs, splenomegaly, hepatomegaly, various embolisms in the central nervous system and liver, fever, and high mortality are present. Other focal infections include cutaneous pustules or ulcers, purulent conjunctivitis, acute iridocyclitis, cervical lymphadenitis, arthritis, osteomyelitis, peritonitis, cholecystitis, and urethritis.


Diagnosis

On the basis of clinical manifestations and results of bacterial isolation and culture with blood or cerebrospinal fluids, diagnosis can be provided.


Treatment

Ampicillin is the best choice for antibacterial therapy, because it is safe for pregnant women and babies, and can reach effective concentrations in the brain. The dose is 50mg/kg once every 6 hours for 3 - 4 weeks in patients with meningitis. Severe patients and immunosuppressed patients are treated with ampicillin in combination with gentamicin. The dose of gentamicin should reach a serum concentration of 5 - 8μg/ml and a cerebral spinal fluid concentration of 1 - 2μg/ml. Patients allergic to penicillin are treated with trimethoprim 160mg plus sulfamethoxazole 800mg intravenously once every 6 - 12 hours.


Prognosis

Pregnant women with listeriosis can develop miscarriage or stillbirth. After early diagnosis and early application of antibiotics, the mortality rate is about 30% in early-onset neonatal listeriosis and about 10% in late-onset neonatal listeriosis. The overall mortality rate of meningitis is about 30%, and higher mortality is present in patients with malignant tumor or low immunity. The mortality rate of lesions of central nervous system or endocarditis can reach 50%.


Prevention

Since listeriosis is infected through the mouth, the importance of dietary hygiene should be emphasized. For instance, raw milk, raw vegetables, and undercooked meat should be avoided. Persons with immune dysfunction should avoid contact with patients with listeriosis. Active treatment of pregnant women with listeriosis can prevent neonatal or fetal infections. When the disease is found in the neonatal room, isolation is needed.