Listeriosis reservoir

Clinical Manifestations

The incubation period for invasive listeriosis (time from ingestion of contaminated food to illness) averages about 11 days; 90% is within 28 days.10 Invasive listeriosis in an immunocompromised adult is most often manifested as bacteremia without an obvious focus. In such cases, patients have nonspecific complaints, such as fever, malaise, myalgia, and back pain. Bacteremia is the form of invasive listeriosis that complicates pregnancy; CNS infection in pregnancy is extremely rare in the absence of other risk factors. Listeriosis during pregnancy may lead to spontaneous abortion or neonatal sepsis, but early antimicrobial therapy may result in the birth of a healthy child. Endocarditis withL. monocytogenes can occur on both native and prosthetic valves and carries a high rate of septic complications.11 Endocarditis, but not bacteremia per se, may be a clue to underlying colon cancer; colonoscopy should be considered in all cases of listerial endocarditis.

Persons in whomL. monocytogenes bacteremia develops may progress to CNS infection (neurolisteriosis), most commonly manifested as meningitis.Listeria has a predilection for infecting brain tissue as well as the meninges, and unlike other common bacterial causes of meningitis, it not infrequently causes encephalitis or brain abscess. Brain abscess as a result of infection byL. monocytogenes exhibits unusual features compared with other bacteria: listerial brain abscess coexists with bacteremia in nearly all cases and with meningitis in one fourth; in addition, abscesses are often subcortical.12

L. monocytogenes is the most common cause of bacterial meningitis in patients with lymphomas, organ transplant recipients, and patients treated with corticosteroids for any reason. Affected persons usually have the classic acute symptoms of meningitis, but the presentation is subacute (>24 hours) in 60% of cases. Nuchal rigidity is absent in 20%. Focal neurologic findings, including ataxia, tremors, myoclonus, and seizures, may be seen, consistent with the tropism ofListeria for brain parenchyma. Gram stain of cerebrospinal fluid (CSF) reveals small gram-positive rods in only about one third of cases. The glucose content in CSF is normal in more than 60% of cases; mononuclear cells predominate in 30%.

Listerial rhombencephalitis is an unusual form of listerial encephalitis that involves the brain stem and, unlike other listerial CNS infections, usually occurs in healthy adults. The typical clinical picture is one of a biphasic illness with a prodrome of fever, headache, nausea, and vomiting lasting about 4 days, followed by the abrupt onset of asymmetrical cranial nerve deficits, cerebellar signs, and hemiparesis or hemisensory deficits or both. Respiratory failure develops in about 40% of patients. Nuchal rigidity is present in about half, and CSF findings are only mildly abnormal, with a positive CSF culture in about 40%. Almost two thirds of patients are bacteremic. Magnetic resonance imaging is superior to computed tomography for demonstrating rhombencephalitis. Mortality is high, and serious sequelae are common in survivors.

Listeriosis

Listeriosis is caused byListeria monocytogenes, a non-spore-forming, short, Gram-positive bacillus. It is an intracellular pathogen that is able to survive and multiply within host phagocytic cells. Listeriosis primarily affects older adults, pregnant women, neonates, and immunocompromised hosts. Listeria is found in soil and decaying vegetable matter. It is also found in the intestinal tracts of several mammals, birds, fish, and crustaceans. In adults, most infections are thought to arise from oral ingestion of contaminated material, leading to intestinal mucosal penetration and systemic infection. Impaired cell-mediated immunity and macrophage function are associated with increased susceptibility to infection with Listeria.107 In pregnant women, the bacterium is able to cross the placenta during maternal bacteremia and infect the fetus. Infection in pregnant women can lead to spontanous abortion, stillbirth, preterm labor, or neonatal infection.

In a systematic review of peer-reviewed literature, the WHO estimated that listeriosis resulted in 23,150 illnesses worldwide in 2010 leading to 5463 deaths. In this review of listeriosis cases, 20.7% were perinatal infections with septicemia occurring in 30.7% of infected neonates.24 Most cases of listeriosis occur as sporadic illnesses, likely after ingestion of contaminated food. Several foodborne outbreaks have also been reported and are associated with a variety of foods. The most common foods implicated in infections are delicatessen meats, hot dogs, soft cheeses, smoked seafood, and pâtés.

Among all organisms causing neonatal sepsis,L. monocytogenes is a relatively uncommon cause. Listeria infection in neonates is classified as early onset or late onset. The signs and symptoms of listeriosis in neonates are indistinguishable from the signs and symptoms of other postnatal bacterial infections. Early-onset disease is most often acquired by transplacental transmission, and affected infants are symptomatic soon after birth. Meconium passage is often associated with intrauterine Listeria infection. Common manifestations of early-onset infection include neonatal sepsis and pneumonia. Late-onset infection may be acquired by vertical transmission from a colonized mother during passage through the birth canal or by transmission from other colonized or infected caregivers. Symptoms usually arise after the first week or two of life. The most common manifestation of late-onset listeriosis is meningitis, often with insidious onset.

As for any neonate with suspected sepsis, blood and CSF cultures should be obtained. In addition, isolation ofL. monocytogenes from cultures of amniotic fluid or placental tissue may support the diagnosis of early-onset disease. Recommended empiric antibiotic treatment for neonatal sepsis includes ampicillin and an aminoglycoside. This regimen provides important coverage for listeriosis, as cephalosporins have no activity againstL. monocytogenes. When infection with Listeria has been confirmed, the antibiotic of choice is ampicillin. The addition of gentamicin is recommended to provide synergy. After the patient demonstrates clinical improvement, gentamicin can be discontinued and ampicillin given alone to complete the remainder of treatment. For all cases of Listeria meningitis, a repeat lumbar puncture should be performed 1-2 days after the start of treatment to confirm sterilization of the CSF. Treatment duration of 10-14 days is recommended for uncomplicated bacteremia. For meningitis, treatment should be continued for 14-21 days. All patients with Listeria meningitis should have neuroimaging obtained near the anticipated end of treatment to determine whether there is parenchymal involvement and whether the patient may require a more prolonged course of treatment.

Prognosis

Neonatal listeriosis accounts for the largest recognizable group of infections caused by L. monocytogenes. Fetal loss with early gestational infection is a recognized complication of maternal infection. In late gestational maternal infection, sparing of the fetus has been reported [266], but it is likely uncommon unless antepartum antibiotic treatment has been given to the mother [267,268].

Although fetal or neonatal infection with L. monocytogenes is known to have a high fatality rate, the long-term morbidity is unclear. Rotheberg and associates [269] found an increased incidence of developmental delay assessed at a mean age of 29.5 months among small (<1250g at birth), Listeria-infected infants who required assisted ventilation. Naege [270], studying children 4 to 7 years after they recovered from early-onset listeriosis, also found increased neurodevelopmental handicaps. Other authors have reported hydrocephalus [271].

In contrast, Evans and coworkers [272] found no evidence of neurodevelopmental sequelae in six of eight survivors studied at a mean age of 15 months and again at 32 months. The two infants with neurodevelopmental sequelae had severe acute perinatal sepsis with meningitis. Both had spastic diplegia. The authors concluded that long-term sequelae after neonatal early-onset listeriosis were uncommon. If meningitis is not present, the outcome may be generally good. The prognosis for infants with late-onset neonatal sepsis and meningitis has not been studied extensively.

Acute General Rx

Epidemiology

Statistical Data on Prevalence and Incidence of the Disease

Listeriosis is reported mainly in the industrialized countries, and data from Africa, Asia, and South America are scarce. The absence of diagnostic and surveillance systems or testing facilities, the high incidence of other pathogens and pathologies, different consumption patterns and dietary habits, or different host susceptibilities are the possible reasons for the lack of data in these continents.

In Europe, the incidence of listeriosis in 2008 was three cases per million inhabitants. A decrease was observed in 2007 and 2008. However, in recent years, an increase in the rate of listeriosis has been reported in countries such as Estonia, Germany, Ireland, Italy, Latvia, Lithuania, Netherlands, Poland, Spain, Sweden, and the UK.

In Canada and in the USA the reported incidence is approximately four and three cases per million inhabitants per year, respectively.

Although listeriosis can cause disease in all populations, the majority of cases (more than 50%) occur in those aged 65 years and more, but most elderly patients often have an underlying immunocompromising condition.

Listeriosis

In nonpregnant adults, L. monocytogenes has been shown to cause meningitis, encephalitis, and septicemia. In rare cases, contact with infected animals has caused focal infections in veterinarians. Although skin lesions are the major symptoms usually observed, endocarditis, arthritis, osteomyelitis, intra-abdominal abscess, and pleuropulmonary infections have also been described, albeit on rare occasions.

Listeriosis can be sporadic or epidemic, with food being the primary vehicle of transmission. While the reported incidence of listeriosis ranges from 0.2 to 8.3 cases per million population in industrialized countries, it is widely accepted that the true rate of the human disease is underestimated. Interestingly, the incubation period of listeriosis can range from 24h to 91 days. The reason for this is not fully understood, but factors such as immune status, bacterial load, genetic predisposition, and other reasons may play a role. Another unresolved issue is the tropism of L. monocytogenes for the central nervous system.

Human listeriosis can be caused by all serotypes of L. monocytogenes. However, the majority of listeriosis cases have been shown to be caused by serotypes 1/2a, 1/2b, and 4b. Further analyses has revealed that serotype 4b is prevalent in many European countries. In North America, serotypes 1/2a (Canada) and 4b (USA) are most often recovered in cases of listeriosis. Again, the reason for the differences observed in serotype and geographical distribution is unclear. Equally, it is not known at present why only three serotypes cause most of the illness.

Etiology and Disease in Humans

Listeriosis is a rare but potentially fatal food-borne illness caused by Listeria monocytogenes, a Gram-positive bacterium found throughout the environment in soil, vegetation, and water supplies. Listeria can survive in acidic and salty foods, and continue to multiply at low temperatures, allowing for growth in poorly refrigerated foods (Jacobson, 2008). Raw milk and products made from raw milk are often the source of infection. The bacteria gain access to the body through ingestion and disseminate hematogenously. Pregnant women, neonates, the elderly, and immunocompromised patients are at highest risk for listeriosis due to impaired T-cell function. The most common clinical manifestations of listeriosis are sepsis and meningoencephalitis (Hof et al., 1997; Levidiotou et al., 2004).

Importance to the Consumer

Listeriosis in humans can take any one of three clinical forms: encephalitis, septicemia, and abortion. Symptoms can range from flulike to more substantial clinical manifestations. For the most part, only L. monocytogenes appears to be pathogenic in humans, whereas other species, including L. ivanovii, have been reported to cause ovine abortions and retard growth in lambs. Listeriosis appears to have a higher mortality rate than other foodborne bacterial pathogens. The mortality rate has been reported to be 20%, but this may be misleading as probably few cases of listeriosis that do not progress past the flulike symptoms are diagnosed correctly. Sensitive populations, including pregnant women, the young, the elderly, and persons with compromised immune systems, need to be diligent in not only avoiding foods that may contain Listeria but also in seeking medical attention when flulike symptoms do not quickly dissipate. People with acquired immunodeficiency syndrome are among the sensitive populations, and fetal abortions are a prevalent outcome in both outbreak and sporadic cases of listeriosis.

There are a number of well-documented outbreaks of listeriosis in humans, all of which involve L. monocytogenes. The most common serotype of L. monocytogenes associated with foodborne illness is type 4B. A variety of foods have been implicated, including, animal-, dairy-, and vegetable-based products. The most common food is soft cheeses, which, due to the nature of their manufacture, are particularly susceptible to contamination by L. monocytogenes. In addition, ready-to-eat foods, which typically are refrigerated after purchase, also have been problematic. Proper in-home preparation of foods, especially hot dogs, can reduce the likelihood of contracting foodborne listeriosis. In 1998, a large outbreak of listeriosis that resulted in a number of deaths and fetal abortions appeared to involve hot dogs and perhaps other ready-to-eat meat products. No conclusive source of contamination has been identified to date.