Listeriosis natural history, complications and prognosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

Listeriosis is commonly transmitted through contaminated food. The clinical presentation of the disease depends on the baseline health status of the patient. Although asymptomatic carriers may be identified, the disease is commonly manifested as a febrile gastroenteritis. Other more invasive manifestations include sepsis of unknown origin, bacteremia, central nervous system (CNS) infection, endocarditis, and focal infections. Possible complications of listeriosis include acute respiratory distress syndrome (ARDS), rhabdomyolysis, acute renal failure, and pneumonia. The prognosis of listeriosis depends on the health status of the host, where healthy older children and adults show the lowest death rate.

Natural History

The majority of cases of listeriosis are sporadic. Although the source is often unknown, contaminated food is the most common vehicle of transmission. Some patients may be transitory carriers of the bacteria without manifesting signs of the disease. Once the bacterium penetrates the gastrointestinal lining, it travels through the bloodstream to otherwise aseptic sites, such as the CNS, the uterus, and sometimes the heart, leading to the following diseases such as:

• Febrile gastroenteritis
• Infection in pregnancy
• Sepsis of unknown origin
• Bacteremia
• CNS infection
• Endocarditis
• Focal infections

The mean incubation period for febrile gastroenteritis following listeriosis is 24 hours, however, it may range from 6 hours up to 10 days. In invasive diseases, the mean incubation period is 35 days, ranging from 1 to 91 days.

Febrile Gastroenteritis

Febrile gastroenteritis accounts for less than 1% of reported bacterial food-born infections, occurring usually after ingestion of a large inoculum of bacteria from contaminated foods. Illness typically occurs 24 hours after ingestion of contaminated food, presenting with symptoms such as fever, nausea, vomiting, and watery diarrhea.

It generally lasts for 2 days and the patient experiences complete recovery from the symptoms. Some patients may be asymptomatic for the disease, while others, immunocompromised, pregnant women and elder patients, in rare cases, present with invasive infection. L. monocytogenes infection should be considered when outbreaks of foodborne gastroenteritis surge and stool cultures fail to identify the pathogen.

Infection in Pregnancy

Pregnant women have greater risk of contracting listeriosis due to a slight impairment of cell-mediated immunity during pregnancy. Listeria is also able to proliferate in the placenta, in hard-to-reach areas for the immune system. Infection occurs more frequently during the third trimester of gestation presenting most commonly with flu-like symptoms, such as fever and chills.

The infection may be mild and the diagnosis can be missed when blood cultures are not obtained. Since bacteremia with no CNS involvement is common among pregnant women with listeriosis, blood cultures should always be obtained in pregnant women who present with fever, with no other possible cause, such as UTI or pharyngitis. Because cell-to-cell transmission facilitates maternal-fetal transmission, listeriosis in pregnant women can result in fetal death, premature birth, or infected newborns.

Among pregnant women with listeriosis, 2/3 of the surviving infants develop clinical neonatal listeriosis.. The newborn also has a great risk of developing granulomatosis infantiseptica, a severe in utero infection secondary to transplacental transmission, which is characterized by the following:

• Disseminated abscesses
• Granulomas in multiple internal organs (brain, lungs, liver, spleen and kidneys)
• Papular or ulcerative skin lesions
• Stillborn infants or death soon after birth

L. monocytogenes is one of the three major causes of neonatal meningitis worldwide. The early diagnosis and treatment of pregnant women infected with Listeria may lead to the birth of a normal healthy child.

Sepsis of Unknown Origin

Sepsis of unknown origin can ccur in patients of all ages. Neonates usually tend to acquire the infection during or after birth. While infection during the first week of life usually manifests as sepsis, infection after the first week of life tends to have more variable manifestations, such as meningitis.

Early onset of sepsis is associated with higher neonatal mortality. In this case, L. monocitogenes can be isolated from conjunctivae, amniotic fluid, meconium, placental blood, with higher concentrations of bacteria in the neonatal lung and gut. These findings suggest that infection is acquired in uterus by inhalation of infected amniotic fluid.

• Listerial meningoencephalitis is more common among neonates after 3 days of age, as well as among immunocompromised and elderly adults.
• Adults with Listerial sepsis are most commonly immunocompromised or elderly and typically present with fever and chills. Septic shock can occur with brain and/or meningeal involvement, leading to meningoencephalitis or cerebritis.

Bacteremia

After the neonatal period, the most common manifestation of listeriosis is bacteremia without any evident focus of infection. The clinical manifestations may include fever, myalgias, and nausea.

Often times, healthy individuals who experience these manifestations do not have blood cultures. Therefore, these individuals a have higher probability of transient bacteremias going undetected.

CNS Infection

Because L. monocytogenes has tropism for the brain stem and meninges, unlike other causes of bacterial meningitis, Listeria tends to cause parenchymal brain infections. Therefore, most patients will experience altered consciousness, seizures and/or movement disorders, and will truly have meningoencephalitis.

CNS infection is commonly manifested by meningoencephalitis, while cerebritis is a less common manifestation. In a study from the Massachusetts General Hospital about CNS listeriosis outside neonatal period and pregnancy, the most common predisposing factor for developing listerial meningitis was malignancy, the second most common factor being transplantation, followed by alcoholism, liver disease, immunosuppression, steroid treatment, diabetes mellitus, and HIV".

Meningoencephalitis

Occurs more frequently in neonates after 3 days of age, in immunocompromised, and elderly patients. The clinical presentation can range from mild fever and mental status changes, to a more aggressive course with coma. There may also be an encephalic component, which will present with focal neurological signs, such as cranial nerve abnormalities, ataxia, and hemiplegia.

Cerebritis/ Encephalitis

Evidence of direct hematogenous invasion of cerebral parenchyma, with or without meningeal involvement, is probably a sign of an early localized infection of the parenchyma, which may eventually progress into brain abscess. Cerebritis may occur along with meningitis in the same patient. In these cases, the clinical picture is dominated by altered consciousness or cognitive disfunction. The disease might also manifest as fever and hemiplegia.

Rhombencephalitis

Rhombencephalitis is a rare manifestation of Listeria CNS infection, and it most commonly affects healthy individuals through the ingestion of food contaminated with Listeria, often in outbreaks. Rhombencephalitis often follows a biphasic course, beginning with headache, fever, nausea and vomiting for the first 4 days. This phase is followed by abrupt onset of asymmetric cranial nerve palsies, ataxia, decreased consciousness, seizures, sensory deficits, and respiratory failure.

In this type of the disease, mortality is high and the survivors likely experience serious sequelae.

Brain abscess

Most cases occur in high risk patients. The subcortical abscesses are mostly located in the thalamus, pons, and/or medulla, sites which are rarely affected by other bacteria..

Spinal cord infection

Rare cases of spinal cord involvement have been reported in listeriosis. When the spinal cord is affected in the setting of acute bacterial meningitis of uncertain etiology, L. monocytogenes should be considered.

Focal Infections

Most focal infections do not have specific characteristics. These infections occur more often in immunocompromised patients, and include:

• Skin or eye infections
• Oculoglandular syndrome, pneumonia, empyema, myocarditis, lymphadenitis, septic arthritis, osteomyelitis and necrotizing fasciitis
• Brain abscess and spinal abscesses, as well as cholecystitis, resulting from hematogenous dissemination
• Acute hepatitis, similar to viral hepatitis, seen in patients with disseminated infections
• Peritonitis, seen in cirrhosis and among continuous ambulatory peritoneal dialysis patients

Endocarditis

Listerial endocarditis usually leads to native and prosthetic valve disease, with an elevated rate of septic complications. Listerial endocarditis alone may be an indicator of a GI tract abnormality, such as cancer.

Complications

Immunosuppressed patients with listeriosis are more likely to develop serious complications, such as life-threatening bacteremia and meningoencephalitis.

Complications of invasive disease include:

• Disseminated intravascular coagulation
• ARDS
• Rhabdomyolysis
• Acute Renal Failure
• Septicemia, meningitis (or meningoencephalitis)
• Encephalitis
• Corneal ulcer
• Pneumonia
• Intrauterine or cervical infection in pregnant women, may result in:

• Spontaneous abortion (2nd/3rd trimester)
• Stillbirth
• Surviving neonates of fetomaternal listeriosis may suffer from:

• Granulomatosis infantiseptica: pyogenic granulomas distributed over the whole body, and the newborn may suffer from physical retardation
• Influenza-like symptoms: including persistent fever, which usually precedes the onset of the aforementioned disorders

• Reinfection (rare)

Prognosis

The prognosis of listeriosis depends on the health status of the host:

• Healthy older children and adults have a lower death rate.
• Listeriosis in a fetus or infant results in a poor outcome with a high death rate.
• Even with prompt treatment, some listeriosis cases result in death. This is particularly likely in older adults and in persons with other medical conditions.