The clinical course and outcome of Listeria monocytogenes meningitis: A retrospective single center study.

BACKGROUND: The aim of the study was to determine clinical manifestations and outcome of Listeria monocytogenes meningitis (LM) and to compare with other forms of bacterial meningitis (BM). MATERIAL AND METHODS: We analyzed records of all adult patients with BM who were hospitalized between January 2010 and December 2017 in the largest neuroinfection center in Poland. RESULTS: Out of 343 analyzed patients with BM 24 were diagnosed to have LM. Patients with LM were older compared to patients with other forms of BM (62 years vs. 57 years, p=0.039), were more likely to have cancer (16.7% vs. 4.7%, p=0.045), receive immunosuppressive treatment (45.8% vs. 10.7%, p<0.001), or be immunocompromised in any way (62.5% vs. 35.5%, p=0.016). Blood tests showed lower WBC (10.7 × 103 cells/µl vs. 15.5 × 103 cells/µl, p=0.004), C-reactive protein (150 mg/L vs. 221 mg/L, p=0,019) and procalcitonin (1.27 ng/mL vs. 3.78 ng/mL, p=0.003) in LM group. Analysis of cerebrospinal fluid showed lower cell count (531.5 cells/µL vs. 1100 cells/µL, p<0.001) and lower chloride (113 mmol/L vs. 117 mmol/L, p=0.036) in patients with LM. In the multiple logistic regression analysis, immunosuppressive therapy was the only variable independently associated with LM (OR:8.72, CI 95%:1.41-64.34, p=0.024). CONCLUSIONS: LM is associated with older age, cancer and immunosuppressive therapy. However, in multivariate analysis only immunosuppressive therapy turned out to be an independent risk factor for LM.

Listeria Meningitis in an Immunocompetent Child: Case Report and Literature Review

We present a case of a 23 month-old boy presenting with fever, irritability and diarrhea who subsequently developed symptoms of photophobia and lethargy. Cerebrospinal fluid culture grew Listeria monocytogenes. Immunology investigations were normal. This patient had a complete and uncomplicated recovery. Listeria meningitis is a rare presentation in immunocompetent children, but should be considered in the setting of diarrhea, failure to respond to cephalosporin therapy, or suspected immunodeficiency.

Histopathology of Listeria Meningitis.

Listeria monocytogenes meningitis is the third most common cause of bacterial meningitis in adults and has high mortality and morbidity rates. We describe the clinical course and score brain pathology of 5 patients who died of listeria meningitis. All patients were immunocompromised and ages ranged between 48 and 76 years. Three cases were confirmed by cerebrospinal fluid culture; one was confirmed by brain culture; and one diagnosis was based on a positive blood culture and neuropathological findings. Mild inflammation of meningeal arteries was found in 3 of 5 cases (60%). Moderate/severe ventriculitis was seen in 4 of 4 cases (100%), abscesses in 3 of 4 cases (75%), mild vascular inflammation in 4 of 5 cases (80%), mild/moderate hemorrhage in 2 of 4 cases (50%), mild/moderate thrombosis of meningeal artery in 3 of 5 cases (60%), and 1 case (25%) showed a moderate infarct. The inflammatory cells present in the meninges were characterized by a mix of monocytes, macrophages, and neutrophils and removal of apoptotic inflammatory cells by macrophages (efferocytosis). Gram stain showed intra- and extracellular presence of rod-shaped bacteria in 3 cases. Pathological examination was characterized by moderate to severe ventriculitis, abscesses and abundant efferocytosis which has been suggested to be exploited by L. monocytogenes for cell-to-cell spread.

Identification of the first case of atypical scrapie in Japan.

A Corriedale ewe was confirmed as the first atypical scrapie case during an active surveillance program for transmissible spongiform encephalopathies in small ruminants in Japan. The animal was homozygous for the AF141RQ haplotype of PRNP. The animal showed clinical neurological signs possibly due to listeriosis before culling. Western blot analysis showed an unusual multiple banded pattern with a low-molecular fragment at ~7 kDa. Histopathology revealed suppurative meningoencephalitis caused by listeriosis in the brainstem. Fine granular to globular immunostaining of disease-associated prion proteins was mainly detected in the neuropil of the spinal tract of the trigeminal nerve and in the white matter of the spinocerebellar tract. Based on these results, this case was conclusively diagnosed as atypical scrapie with encephalitic listeriosis.

An unusual presentation of paediatric Listeria meningitis with selective spinal grey matter involvement and acute demyelinating polyneuropathy.

BACKGROUND: Paediatric Listeria meningitis is rare, especially in immuno-competent children, but associated with significant mortality and morbidity and frequent complications. METHODS: We report an unusual case of Listeria meningitis in a previously healthy 35 month-old girl with selective spinal grey matter involvement and demyelination in neurophysiological studies. Despite adequate antibiotic treatment, the case was initially complicated by ventriculitis, hydrocephalus and tonsillar herniation through the foramen magnum, requiring external ventricular drainage and subsequent ventriculoperitoneal shunt insertion. Paucity of movements, hypotonia, areflexia and bladder dysfunction then became evident. RESULTS: Electromyogram and nerve conduction studies showed acute inflammatory demyelinating polyneuropathy and the patient received intravenous immunoglobulin followed by corticosteroids. MRI scans with contrast revealed extensive whole cord selective grey matter signal changes. She required extensive neurorehabilitation, making gradual (but incomplete) recovery. CONCLUSION: Spinal cord involvement is rare in neuro-listeriosis and there no previous paediatric reports of Listeria-related myelitis or demyelinating polyneuropathy. The mechanism behind these presentations is unclear but an auto-immune response to the infection might be considered.

The clinical features, diagnosis, treatment, and prognosis of neuroinvasive listeriosis: a multinational study.

The aim of this study was to determine the independent risk factors, morbidity, and mortality of central nervous system (CNS) infections caused by Listeria monocytogenes. We retrospectively evaluated 100 episodes of neuroinvasive listeriosis in a multinational study in 21 tertiary care hospitals of Turkey, France, and Italy from 1990 to 2014. The mean age of the patients was 57 years (range, 19-92 years), and 64% were males. The all-cause immunosuppression rate was 54 % (54/100). Forty-nine (49 %) patients were referred to a hospital because of the classical triad of symptoms (fever, nuchal rigidity, and altered level of consciousness). Rhombencephalitis was detected radiologically in 9 (9 %) cases. Twenty-seven (64 %) of the patients who had cranial magnetic resonance imaging (MRI) performed had findings of meningeal and parenchymal involvement. The mean delay in the initiation of specific treatment was 6.8 ± 7 days. Empiric treatment was appropriate in 52 (52 %) patients. The mortality rate was 25 %, while neurologic sequelae occurred in 13 % of the patients. In the multivariate analysis, delay in treatment [odds ratio (OR), 1.07 [95 % confidence interval (CI), 1.01-1.16]] and seizures (OR, 3.41 [95 % CI, 1.05-11.09]) were significantly associated with mortality. Independent risk factors for neurologic sequelae were delay in treatment (OR, 1.07 [95 % CI, 1.006-1.367]) and presence of bacteremia (OR, 45.2 [95 % CI, 2.73-748.1]). Delay in the initiation of treatment of neuroinvasive listeriosis was a poor risk factor for unfavorable outcomes. Bacteremia was one of the independent risk factors for morbidity, while the presence of seizures predicted worse prognosis. Moreover, the addition of aminoglycosides to ampicillin monotherapy did not improve patients' prognosis.

Listeria monocytogenes sequence type 6 and increased rate of unfavorable outcome in meningitis: epidemiologic cohort study.

BACKGROUND: We analyzed clinical characteristics, treatment, genetic diversity, and outcome of 92 adults with Listeria monocytogenes meningitis included in 2 prospective nationwide cohort studies. METHODS: Episodes of community-acquired listerial meningitis confirmed by cerebrospinal fluid culture were included from 1998 to 2002 and 2006 to 2012. We compared patients and pathogen characteristics between cohorts and identified predictors for an unfavorable outcome according to the Glasgow Outcome Scale. RESULTS: Thirty episodes were included from 1998 to 2002 and 62 from 2006 to 2012; clinical and laboratory characteristics on admission were similar between cohorts. However, the rate of unfavorable outcome increased from 27% in the 1998-2002 cohort to 61% in the 2006-2012 cohort (P = .002). Differences between cohorts were increased use of adjunctive dexamethasone therapy (0% in 1998-2002 vs 53% in 2006-2012; P < .001) and emergence of infection by L. monocytogenes genotype sequence type 6 (ST6; 4% in 1998-2002 vs 29% in 2006-2012; P = .009). Multivariate regression analysis identified infection with L. monocytogenes ST6 as the sole predictor of unfavorable outcome (odds ratio, 3.77; 95% confidence interval, 1.07-13.33). Patients infected with genotypes other than ST6 also had an increased rate of unfavorable outcome over time (P = .03). CONCLUSIONS: The rate of unfavorable outcome among adults with listerial meningitis has increased over a 14-year period, from 27% to 61%. The emerging L. monocytogenes genotype ST6 was identified as the main factor leading to poorer prognosis. Adjunctive dexamethasone may be discontinued if L. monocytogenes is identified, as there is no proven benefit in Listeria meningitis.

Stereotactic biopsy and drainage of a brainstem abscess caused by Listeria monocytogenes.

Listerial rhombencephalitis and brain abscesses are rare, but potentially life-threatening conditions. Early initiation of antibiotic therapy is crucial, but establishing the diagnosis of listerial brainstem abscess can be difficult. Stereotactic biopsy and drainage of space-occupying abscesses of the brainstem should be considered especially in cases of rapid clinical deterioration. We successfully performed stereotactic biopsy and drainage of a listerial brainstem abscess in a 42-year-old male patient who deteriorated despite antibiotic treatment, demonstrating that this approach is suitable in such patients.

Atypical cerebral listeriosis associated with Listeria innocua in a beef bull.

Natural infections of cattle associated with Listeria innocua have not been reported. This report describes the first case of cerebral listeriosis in a bull due to Listeria innocua. The animal presented neurological signs characterized by weakness, incoordination and recumbency. Histopathologic evaluation of brain tissue revealed multifocal microabscesses, perivascular lymphocytic cuffing, vasculitis, oedema and haemorrhages. All lesions extended from the medulla oblongata to the basal nuclei/parietal cortex area. Indirect immunohistochemistry labelled for Listeria sp. in the brain tissue, but not for Listeria monocytogenes, neurotropic Flaviviruses, BVDV, bovine Herpesvirus 1, Chlamydophila spp. and Histophilus somni. PCR was negative for ovine herpesvirus. L. innocua was isolated from brainstem and identified by biochemical tests (Camp and beta-hemolysis negative). Subsequently, the species was confirmed by a duplex PCR and minisequencing assays. L. innocua should be histologically considered as a differential diagnosis of thrombotic meningoencephalitis, malignant catarrhal fever and cerebral listeriosis due to L. monocytogenes in cattle.

[Meningitis due to Listeria monocytogenes in adults]. / Meningitis por Listeria monocytogenes en adultos.

INTRODUCTION: Listeria monocytogenes is the third most common cause of community-acquired bacterial meningitis in adults. AIMS: To describe the characteristics of meningitis caused by Listeria (LM) in adults and to compare them with those of meningitis due to other causations (nLM). PATIENTS AND METHODS: A retrospective analysis of a series of hospital cases was conducted, including patients aged between ≥ 14 years diagnosed with LM in a referral hospital between 1982 and 2011. RESULTS: The study involves 16 cases of LM, 12.1% of the cases of community-acquired meningitis with an identified aetiology. Predisposing factors were age (mean of 65 versus 52 years; p = 0.019) and immunosuppression/comorbidity (62.5% versus 3.4%; p < 0.001), treatment with corticoids (37.5%) and chronic liver disease (25%) being the most frequent. The classical triads of acute bacterial meningitis, clinical features and analysis of the cerebrospinal fluid (CSF) were observed in 50 and 75% of the cases, respectively. Patients with LM presented lower leukocyte counts in CSF, a lower percentage of neutrophils, a greater frequency of lymphocytic pleocytosis and a lower frequency of Gram stain positive than those with nLM. The mortality rate was 12.5%, similar to that of patients with nLM. CONCLUSIONS: LM mainly affects patients who are immunosuppressed or with comorbidity, as well as elderly patients, although it may occur in the absence of risk factors. Clinically it does not differ from other causes of meningitis, but the initial CSF study may suggest it. Its mortality rate is similar to that of meningitis due to other aetiologies.

Meningoencephalitis due to Listeria monocytogenes in a pregnant rhesus macaque (Macaca mulatta).

We here report a spontaneous case of meningoencephalitis due to Listeria monocytogenes in an adult primiparous rhesus macaque (Macaca mulatta) during an outbreak of listeriosis in an outdoor enclosure. Clinical signs included tremors, abnormal posture, and altered mental status. Hematology and analyses of cerebrospinal fluid were consistent with bacterial infection. Pure cultures of L. monocytogenes were recovered from the placenta-abortus, cerebrospinal fluid, and brain tissue. The macaque did not respond to treatment and was euthanized. Histopathologic examination of the brain revealed acute meningoencephalitis. This case represents an unusual clinical and pathologic presentation of listeriosis in a nonhuman primate in which the dam and fetus both were affected.

Clues to diagnosing culture negative Listeria rhombencephalitis.

A previously healthy 35-year-old Caucasian woman developed left body (including facial) hemianaesthesia, asymmetrical lower cranial nerve palsies and cerebellar signs after a 4-day history of headache, nausea and vomiting. Serial blood and cerebrospinal fluid (CSF) cultures returned negative for a culprit organism. CSF examination revealed a lymphocytic pleocytosis and an elevated protein count. CSF cytological examination identified plasma cells. MRI of brain showed multiple ring-enhancing 'abscess-like' lesions in the brainstem and upper cervical cord together with abnormal meningeal enhancement. A decision was made to treat her empirically for Listeria rhombencephalitis to which she responded completely. CSF PCR eventually returned positive for Listeria monocytogenes. This case illustrates the utility of clinical features, MRI, CSF cytology and PCR in diagnosis and treatment of culture negative L monocytogenes rhombencephalitis in an immunocompetent individual.

Targeting of the central nervous system by Listeria monocytogenes.

Among bacteria that reach the central nervous system (CNS), Listeria monocytogenes (Lm) is one of deadliest, in human and ruminant. This facultative intracellular bacterium has the particularity to induce meningitis, meningoencephalitis and rhombencephalitis. Mechanisms by which Lm accesses the CNS remain poorly understood, but two major routes of infection have been proposed, based on clinical, in vitro and in vivo observations. A retrograde neural route is likely to occur in ruminants upon crossing of the oral epithelium, and this probably accounts for the observation that Lm induces almost exclusively rhombencephalitis in these animals. In contrast, the hematogenous route is likely the most frequent in human, in whom bacteria circulating in the blood, either free or associated with leukocytes are thought to breach the blood-brain barrier. New animal models that faithfully reproduce the hallmarks of human neurolisterisosis will allow addressing the molecular mechanisms underlying Lm ability to induce CNS disease, and improve our understanding of the pathophysiology of this deadly infection.

[Unusual location of a brain abscess due to Listeria monocytogenes]. / Abcès cérébral à Listeria monocytogenes de localisation inhabituelle.

Here we report a case of sustentorial brain abscess due to Listeria monocytogenes. Blood culture and procalcitonine blood measurement were negative. L. monocytogenes was isolated from CSF after inoculation in Castañeda medium.

Matrix metalloproteinase expression in sheep with listerial meningoencephalitis.

Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of several central nervous system (CNS) diseases. In this study, we investigated the presence of Listeria monocytogenes antigens and detected the expression of MMP-9 and MMP-7 in the brains of 22 sheep with clinical signs and histopathological findings characteristic of listerial meningoencephalitis. Archived sections from the brainstem, cerebrum, and cerebellum were stained for immunohistochemistry. L. monocytogenes antigens were located mainly in the cytoplasm of neutrophils and some macrophages and/or extracellularly within microabscesses of the brainstem. MMP-9 was mainly immunolocalised in the endothelial cells, microglial cells, and neurons especially in inflammatory areas. MMP-7 immunoreactivity was detected in perivascular cuffs, microglial cells, and only a few neurons. Overall, immunohistochemistry in formalin-fixed, paraffin-embedded tissues is a useful tool for the diagnosis of encephalitic listeriosis caused by L. monocytogenes, and MMP-9 and MMP-7 may contribute to the pathogenesis of listerial meningoencephalitis.

Listeria monocytogenes: a rare complication of ventriculoperitoneal shunt in children.

We report a case of ventriculoperitoneal (VP) shunt infection in a 3-year-old boy caused by the food-borne pathogen Listeria monocytogenes, subsequent to acute peritonitis. This unusual presentation of central nervous system (CNS) listeriosis underlines the ability of the bacteria to form and survive within biofilms on indwelling medical devices. Bacterial persistence may lead to treatment failure and spreading. We highlight the helpfulness of specific quantitative real-time PCR for the hly gene (PCR-hly) for the diagnosis and follow-up of such infections in detecting bacterial persistence within medical devices despite effective antibiotic treatment. Only the surgical replacement of the VP shunt will resolve the infection.

Interleukin-1 receptor type 1 is essential for control of cerebral but not systemic listeriosis.

Listeria monocytogenes may infect the central nervous system and several peripheral organs. To explore the function of IL-1 receptor type 1 (IL-1R1) in cerebral versus systemic listeriosis, IL-1R1(-/-) and wild-type mice were infected either intracerebrally or intraperitoneally with L. monocytogenes. After intracerebral infection with various numbers of attenuated Listeria, IL-1R1(-/-) mice succumbed due to an insufficient control of intracerebral Listeria, whereas all wild-type mice survived, efficiently restricting growth of Listeria. IL-1R1(-/-) mice recruited increased numbers of leukocytes, especially granulocytes, to the brain compared with wild-type mice. In contrast, both IL-1R1(-/-) and wild-type mice survived a primary and secondary intraperitoneal infection with Listeria without differences in the hepatic bacterial load. In addition, both strains developed similar frequencies of Listeria-specific CD4 and CD8 T cells after primary and secondary intraperitoneal infection. However, an intraperitoneal immunization before intracerebral challenge infection neither protected IL-1R1(-/-) mice from death nor reduced the intracerebral bacterial load, although numbers of intracerebral Listeria-specific CD4 and CD8 T cells and levels of inducible nitric oxide synthase, tumor necrosis factor, and interferon-gamma mRNA were identical in IL-1R1(-/-) and wild-type mice. Collectively, these findings illustrate a crucial role of IL-1R1 in cerebral but not systemic listeriosis.

TNF is important for pathogen control and limits brain damage in murine cerebral listeriosis.

Cerebral listeriosis is a life-threatening disease. However, little is known about the bacterial virulence factors responsible for the severe course of disease and the factors of the immune system contributing to the control of Listeria monocytogenes (LM) or even to the damage of the brain. To analyze the importance of the actA gene of LM, which mediates cell-to-cell spread of intracellular LM, the function of TNF in murine cerebral listeriosis was studied. C57BL/6 mice survived an intracerebral (i.c.) infection with actA-deficient LM, but succumbed to infection with wild-type (WT) LM. Upon infection with actA-deficient LM, macrophages and microglial cells rapidly, and later LM-specific CD4 and CD8 T cells, produced TNF. In contrast to WT mice, TNF-deficient animals succumbed to the infection within 4 days due to failure of control of LM. Histology identified a more severe meningoencephalitis, brain edema, and neuronal damage, but a reduced inducible NO synthase expression in TNF-deficient mice. Reciprocal bone marrow chimeras between WT and TNF-deficient mice revealed that hematogenously derived TNF was essential for survival, whereas TNF produced by brain-resident cells was less important. Death of TNF-deficient mice could be prevented by LM-specific T cells induced by an active immunization before i.c. infection. However, brain pathology and inflammation of immunized TNF-deficient mice were still more severe. In conclusion, these findings identify a crucial role of TNF for the i.c. control of LM and survival of cerebral listeriosis, whereas TNF was not responsible for the destruction of brain tissue.