Interferon gamma constrains type 2 lymphocyte niche boundaries during mixed inflammation.

Allergic immunity is orchestrated by group 2 innate lymphoid cells (ILC2s) and type 2 helper T (Th2) cells prominently arrayed at epithelial- and microbial-rich barriers. However, ILC2s and Th2 cells are also present in fibroblast-rich niches within the adventitial layer of larger vessels and similar boundary structures in sterile deep tissues, and it remains unclear whether they undergo dynamic repositioning during immune perturbations. Here, we used thick-section quantitative imaging to show that allergic inflammation drives invasion of lung and liver non-adventitial parenchyma by ILC2s and Th2 cells. However, during concurrent type 1 and type 2 mixed inflammation, IFNγ from broadly distributed type 1 lymphocytes directly blocked both ILC2 parenchymal trafficking and subsequent cell survival. ILC2 and Th2 cell confinement to adventitia limited mortality by the type 1 pathogen Listeria monocytogenes. Our results suggest that the topography of tissue lymphocyte subsets is tightly regulated to promote appropriately timed and balanced immunity.

Increased Listeria monocytogenes Dissemination and Altered Population Dynamics in Muc2-Deficient Mice.

The mucin Muc2 is a major constituent of the mucus layer that covers the intestinal epithelium and creates a barrier between epithelial cells and luminal commensal or pathogenic microorganisms. The Gram-positive foodborne pathogen Listeria monocytogenes can cause enteritis and also disseminate from the intestine to give rise to systemic disease. L. monocytogenes can bind to intestinal Muc2, but the influence of the Muc2 mucin barrier on L. monocytogenes intestinal colonization and systemic dissemination has not been explored. Here, we used an orogastric L. monocytogenes infection model to investigate the role of Muc2 in host defense against L. monocytogenes Compared to wild-type mice, we found that Muc2-/- mice exhibited heightened susceptibility to orogastric challenge with L. monocytogenes, with higher mortality, elevated colonic pathology, and increased pathogen burdens in both the intestinal tract and distal organs. In contrast, L. monocytogenes burdens were equivalent in wild-type and Muc2-/- animals when the pathogen was administered intraperitoneally, suggesting that systemic immune defects related to Muc2 deficiency do not explain the heightened pathogen dissemination observed in oral infections. Using a barcoded L. monocytogenes library to measure intrahost pathogen population dynamics, we found that Muc2-/- animals had larger pathogen founding population sizes in the intestine and distal sites than observed in wild-type animals. Comparisons of barcode frequencies suggested that the colon becomes the major source for seeding the internal organs in Muc2-/- animals. Together, our findings reveal that Muc2 mucin plays a key role in controlling L. monocytogenes colonization, dissemination, and population dynamics.

Clinical and molecular epidemiology of human listeriosis in Taiwan.

OBJECTIVE: To determine serogroups, multilocus sequence typing (MLST) of Listeria monocytogenes isolates and analyze clinical characteristics of these clones focusing on non-perinatal cases. METHODS: From 2000 to 2015, we analyzed 123 human listeriosis cases at a medical center in northern Taiwan using PCR serogrouping, MLST, and clinical presentations. RESULTS: The annual incidence of listeriosis increased since 2005 with a peak in 2008 (0.2 per 1000 admission) and decreased thereafter. Of the 115 non-perinatal listeriosis cases, we found a male predominance (60%) with an average age of 63.9 years old (standard deviation: 15.3 years), and almost all patients had underlying conditions including malignancies (61.7%), steroid usage (39.1%), diabetes mellitus (31.3%), renal insufficiency (27.8%), and liver cirrhosis (17.4%). Clinical presentations included bacteremia (74.8%), neurolisteriosis (20.0%), and spontaneous bacterial peritonitis (5.2%). The most frequently identified serogroup-sequence types (ST) were IIB-ST87 (30.9%), followed by IIA-ST378 (16.3%) and IIA-ST155 (14.6%). The 30-day all-cause mortality of non-perinatal listeriosis was 25.2% and was associated with age (Hazard ratio: 1.04, 95% C.I. = 1.01-1.07, p = 0.021), steroid usage (Hazard ratio: 2.54, 95% C.I. = 1.06-6.11, p = 0.038) and respiratory distress at presentation (Hazard ratio: 2.59, 95% C.I. = 1.05-6.39, p = 0.038); while no association was found with serogroups (IIA, IIB, and IVB) or three major ST types by multivariable analysis. All 8 mothers of perinatal listeriosis patients survived and three neonates died (mortality, 37.5%), and IIB-ST87 was the major type (62.5%). CONCLUSION: Predominant strains in Taiwan could cause significant morbidity and mortality. Further disease monitoring and source surveillance are warranted despite a declining trend of human listeriosis in Taiwan.

Listeria monocytogenes infections: Analysis of 41 patients / Infección por Listeria monocytogenes: análisis de 41 pacientes

OBJECTIVE: We describe and analyze Listeria-related demographics and clinical features to determine the predisposing conditions for severe infections. METHODS: We performed a retrospective study using positive isolation of Listeria monocytogenes from blood, cerebrospinal fluid, and other organic fluids. Electronic health records were used to determine the epidemiological and clinical features of infections caused by L. monocytogenes. Mortality and sepsis were considered dependent variables in the statistical analyses. RESULTS: We included 41 patients in an observation period of 15 years (2003-2018), with an annual incidence rate of 1.3 cases per 100,000 population. Three main population profiles were identified: newborns, pregnant women, and other adults (17.1%, 12.2%, and 82.9%, respectively). Neuroinvasive infection was present in 17 patients (41.5%). In both univariate and multivariate analyses, neurological infections, whether meningoencephalitis, rhombencephalitis, or brain abscesses, were the main risk factors for severe forms of Listeria-related infections (odds ratio 1.8, 95% CI 1.52-2.14, p = 0.01). Malignancies, whether solid tumors or hematological neoplasms, immunosuppression, and chronic diseases were not related to either mortality or severe clinical syndromes. CONCLUSION: Infections caused by L. monocytogenes were uncommon but could cause severe sepsis and mortality, especially in susceptible populations. Our study focused on neurological involvement and severe invasive forms of listeriosis. Neuroinvasive forms were the most important risk factors for severe illness but not for mortality

INTRODUCCIÓN: Describir y analizar las características demográficas y clínicas de las infecciones por Listeria para determinar los factores predisponentes para infecciones severas. MÉTODOS: Diseñamos un estudio retrospectivo utilizando los aislamientos positivos de Listeria monocytogenes en sangre, líquido cefalorraquídeo u otros fluidos orgánicos. Se obtuvieron los registros electrónicos para conseguir las características clínicas y epidemiológicas de las infecciones causadas por L. monocytogenes. Mortalidad y sepsis fueron las variables dependientes en los análisis estadísticos. RESULTADOS: Se incluyeron 41 pacientes en un período de 15 años (2003-2018), con una incidencia anual de 1,3 casos por cada 100.000 habitantes. Identificamos tres perfiles de población: neonatos, mujeres embarazadas y resto de adultos (el 17,1%, el 12,2% y el 82,9%, respectivamente). Las formas neuroinvasivas se identificaron en 17 pacientes (41,5%). Tanto en los análisis univariados como en los multivariados, las infecciones neurológicas, bien meningoencefalitis, rombencefalitis o abscesos cerebrales, fueron los principales factores de riesgo para considerar formas severas de infección por Listeria (odds ratio 1,8; IC 1,52-2,14, p = 0,01). Las neoplasias sólidas o hematológicas, la inmunosupresión o las enfermedades crónicas no estuvieron relacionadas ni con la mortalidad ni con la presencia de severidad en la infección. CONCLUSIÓN: Las infecciones causadas por L. monocytogenes son infrecuentes, pero son causa de sepsis severa y mortalidad en poblaciones susceptibles. Nuestro estudio estuvo dirigido a la infección neuroinvasiva y otras formas graves. La forma neuroinvasiva fue el factor de riesgo más importante asociado a la infección severa, pero no a la mortalidad

Aspectos actuales de la listeriosis / Current aspects of listeriosis

La importancia de la listeriosis no está suficientemente reconocida. Su incidencia general se muestra estable en los últimos años, pero con una tendencia al alza en mayores de 65 años, también en mortalidad. La listeriosis es una enfermedad transmitida por alimentos que ocurre generalmente en forma de casos esporádicos; sin embargo, las nuevas técnicas de tipificación molecular han puesto de manifiesto la existencia de brotes epidémicos no sospechados con anterioridad. La enfermedad presenta un periodo de incubación variable y relacionado con la presentación clínica. La bacteriemia y la neurolisteriosis son las formas clínicas predominantes, aunque en la actualidad el principal interés se focaliza en el manejo de las infecciones focales y las asociadas a dispositivos protésicos. La listeriosis es un problema significativo para la industria alimentaria, y muchos países han introducido legislación para controlar la incidencia de la enfermedad

The importance of listeriosis is not sufficiently recognised. The general incidence of infection has been stable in recent years, but with an upward trend in people over 65, also in mortality. Listeriosis is a foodborne disease that generally occurs in the form of sporadic cases; however, new molecular typing techniques have revealed the existence of epidemic outbreaks not previously suspected. The disease has a variable incubation period, which is related to the clinical presentation. Bacteraemia and neurolisteriosis are the predominant clinical forms, although at present, the main interest is focused on the management of focal infections and those associated with prosthetic devices. Listeriosis is a significant problem for the food industry, and many countries have introduced legislation to control the incidence of the disease

Outbreak of Listeriosis in South Africa Associated with Processed Meat.

BACKGROUND: An outbreak of listeriosis was identified in South Africa in 2017. The source was unknown. METHODS: We conducted epidemiologic, trace-back, and environmental investigations and used whole-genome sequencing to type Listeria monocytogenes isolates. A case was defined as laboratory-confirmed L. monocytogenes infection during the period from June 11, 2017, to April 7, 2018. RESULTS: A total of 937 cases were identified, of which 465 (50%) were associated with pregnancy; 406 of the pregnancy-associated cases (87%) occurred in neonates. Of the 937 cases, 229 (24%) occurred in patients 15 to 49 years of age (excluding those who were pregnant). Among the patients in whom human immunodeficiency virus (HIV) status was known, 38% of those with pregnancy-associated cases (77 of 204) and 46% of the remaining patients (97 of 211) were infected with HIV. Among 728 patients with a known outcome, 193 (27%) died. Clinical isolates from 609 patients were sequenced, and 567 (93%) were identified as sequence type 6 (ST6). In a case-control analysis, patients with ST6 infections were more likely to have eaten polony (a ready-to-eat processed meat) than those with non-ST6 infections (odds ratio, 8.55; 95% confidence interval, 1.66 to 43.35). Polony and environmental samples also yielded ST6 isolates, which, together with the isolates from the patients, belonged to the same core-genome multilocus sequence typing cluster with no more than 4 allelic differences; these findings showed that polony produced at a single facility was the outbreak source. A recall of ready-to-eat processed meat products from this facility was associated with a rapid decline in the incidence of L. monocytogenes ST6 infections. CONCLUSIONS: This investigation showed that in a middle-income country with a high prevalence of HIV infection, L. monocytogenes caused disproportionate illness among pregnant girls and women and HIV-infected persons. Whole-genome sequencing facilitated the detection of the outbreak and guided the trace-back investigations that led to the identification of the source.

Clinical features of neonatal listeriosis in Taiwan: A hospital-based study.

BACKGROUND: Neonatal listeriosis is a major cause of mortality in newborn; however, there is limited information about this disease in Taiwan. The aim of our study was to identify the outcome determinants, clinical features, and incidence of pregnancy-associated listeriosis, which includes both neonatal and maternal listeriosis. METHODS: We retrospectively analyzed the medical records of neonatal and maternal patients with pregnancy-associated listeriosis at two hospitals in Taiwan from January 2000 to December 2018. Listeriosis was indicated by positive Listeria monocytogenes culture. RESULTS: Our study examined 18 neonates and 19 mothers. The neonatal and fetal death rate was 24%. All five cases of fetal losses or neonatal deaths occurred before 29 weeks of gestational age. The annual incidence of confirmed neonatal listeriosis increased significantly from 0.94/10,000 neonatal inpatients in 2000-2011 to 5.45/10,000 neonatal inpatients in 2012-2018 (p = 0.026). Clinical presentations of neonatal listeriosis included respiratory distress (85%), leukocytosis or leukopenia (77%), bandemia (69%), thrombocytopenia (77%), hypocalcemia (100%) and elevated C-reactive protein (CRP) levels (92%). Lower gestation correlated with a higher fatality rate (p = 0.002). Among the maternal cases investigated, 67% had a diagnosis of listeriosis, and 72% presented with fever. However, only 21% of the 19 mothers received complete antepartum ampicillin treatment. CONCLUSIONS: The incidence of neonatal listeriosis is increasing, especially in preterm neonates. Maternal listeriosis should be adequately treated with appropriate empirical antibiotics.

Outcomes of neonates with listeriosis supported with extracorporeal membrane oxygenation from 1991 to 2017.

BACKGROUND: Listeriosis may cause severe disease in fetuses and neonates. The outcomes of critically ill neonates with early-onset listeriosis requiring extracorporeal membrane oxygenation (ECMO) from 1975 to 1991 have been reported. OBJECTIVE: To update the characteristics and outcomes of neonates with listeriosis supported by ECMO. STUDY DESIGN: Retrospective study of neonates with culture-proven listeriosis reported to the Extracorporeal Life Support Organization Registry between 1991 and 2017. Comparisons were made between this cohort and the case series from 1975-1991. RESULTS: Twenty-two neonates had culture-proven Listeria monocytogenes infection and required ECMO support. Eight-six percent survived to discharge, compared with 67% in the previous cohort (p = 0.2). The median ECMO duration was 131 h, compared with 209 h in the previous cohort (p = 0.1). Nonsurvivors had a significantly lower pre-ECMO pH (6.91 vs 7.31, p = 0.0006). CONCLUSION: The survival of neonates with listeriosis supported with ECMO is high, supporting the use of ECMO as rescue therapy for this condition.

Antibiotic treatment for invasive nonpregnancy-associated listeriosis and mortality: a retrospective cohort study.

Little evidence exists addressing the clinical value of adding gentamicin to ampicillin for invasive listeriosis. A multicenter retrospective observational study of nonpregnant adult patients with invasive listeriosis (primary bacteremia, central nervous system (CNS) disease, and others) in 11 hospitals in Israel between the years 2008 and 2014 was conducted. We evaluated the effect of penicillin-based monotherapy compared with early combination therapy with gentamicin, defined as treatment started within 48 h of culture results and continued for a minimum of 7 days. Patients who died within 48 h of the index culture were excluded. The primary outcome was 30-day all-cause mortality. A total of 190 patients with invasive listeriosis were included. Fifty-nine (30.6%) patients were treated with early combination therapy, 90 (46.6%) received monotherapy, and 44 (22.8%) received other treatments. Overall 30-day mortality was 20.5% (39/190). Factors associated with mortality included lower baseline functional status, congestive heart failure, and higher sequential organ failure assessment score. Source of infection, treatment type, and time from culture taken date to initiation of effective therapy were not associated with mortality. In multivariable analysis, monotherapy was not significantly associated with increased 30-day mortality compared with early combination therapy (OR 1.947, 95% CI 0.691-5.487). Results were similar in patients with CNS disease (OR 3.037, 95% CI 0.574-16.057) and primary bacteremia (OR 2.983, 95% CI 0.575-15.492). In our retrospective cohort, there was no statistically significant association between early combination therapy and 30-day mortality. A randomized controlled trial may be necessary to assess optimal treatment.

Listeria monocytogenes-associated endovascular infections: A study of 71 consecutive cases.

BACKGROUND: Listeria monocytogenes-associated endovascular infections are not well characterized. METHODS: Retrospective study of 71 culture-proven cases reported to the French National Reference Center for Listeria from 1993 to 2018. RESULTS: Seventy-one cases were identified: 42 with vascular aneurysms/prosthetic infections, 27 with endocarditis, 2 with both. Fifty-eight were men (82%); median age was 75 years [46-92]; 93% reported co-morbidities (66/71), including 50% with immunosuppressive conditions. Vascular infections consisted of infected aneurysms (68%) or prosthetic graft infections (32%); vascular rupture was reported in 25/42 (60%). Tissue samples grew L. monocytogenes in 98% (43/44) and blood cultures in 64% (27/42). Endocarditis cases involved prosthetic or native valves or intracardiac devices in respectively 62% (18/29), 28% (8/29) and 10% (3/29). Infected valves were aortic (62%, 16/26), mitral (31%, 8/26) or both (8%, 2/26); 38% patients required surgery; 45% displayed heart failure; 17% had concomitant neurolisteriosis. In-hospital mortality in vascular infections was 12% (5/42) and 41% (12/29) for Lm-associated endocarditis. CONCLUSIONS: Endovascular listeriosis is a rare but severe infection. It manifests as vascular infections and endocarditis, mostly in older patients with vascular or cardiac valve prosthetic devices and co-morbidities. Mortality in Lm-associated endocarditis is twice higher than with other pathogens, requiring prompt recognition and treatment.

Adverse events with fatal outcome associated with alemtuzumab treatment in multiple sclerosis.

OBJECTIVE: Sporadic fatal adverse events have been reported during treatment of multiple sclerosis with alemtuzumab. To provide a systematic overview, we searched the centralized European Medicines Agency database of suspected adverse reactions related to medicinal products (EudraVigilance) for fatal adverse events associated with treatment with alemtuzumab (Lemtrada®) for multiple sclerosis. Four independent reviewers with expertise on MS, clinical immunology, infectious diseases and clinical pharmacology reviewed the reports, and scored the likelihood for causality. RESULTS: We identified nine cases with a probable and one case with a possible causal relationship between alemtuzumab treatment and a fatal adverse event. Six of these patients died within one month after treatment; one from intracerebral hemorrhage, two from acute multiple organ failure and septic shock, one from listeriosis, one from pneumonia and one from agranulocytosis. Four patients died several months after administration of alemtuzumab from either autoimmune hepatitis, immune-mediated thrombocytopenia, autoimmune hemolytic anemia or agranulocytosis. Four of the 10 cases had been published previously in case reports or congress abstracts. Fatal adverse events related to treatment with alemtuzumab occur more frequently than previously published in the literature. A significant proportion occurs in the first month after treatment.

Mortality risk factors for listeriosis - A 10 year review of non-pregnancy associated cases in England 2006-2015.

LISTERIOSIS: is a foodborne illness that can result in septicaemia, Central Nervous System (CNS) disease, foetal loss and death in high risk patients. OBJECTIVES: To analyse the demographic trends, clinical features and treatment of non-perinatal listeriosis cases over a ten year period and identify mortality-associated risk factors. METHODS: Reported laboratory-confirmed non-pregnancy associated cases of listeriosis between 2006 and 2015 in England were included and retrospectively analysed. Multivariate logistic regression analysis was performed to determine independent risk factors for mortality. RESULTS: 1357/1683 reported cases met the inclusion criteria. Overall all-cause mortality was 28.7%; however, mortality rates declined from 42.1% to 20.2%. Septicaemia was the most common presentation 69.5%, followed by CNS involvement 22.4%. CNS presentations were significantly associated with age < 50 years, and septicaemia with older age. Age > 80 years (OR 3.32 95% CI 1.92-5.74), solid-organ malignancy (OR 3.42 95% CI 2.29-5.11), cardiovascular disease (OR 3.30 95% CI 1.64-6.63), liver disease (OR 4.61 95% CI 2.47-8.61), immunosuppression (OR 2.12 95% CI 1.40-3.21) and septicaemia (OR 1.60 95% CI 1.17-2.20) were identified as independent mortality risk factors. CONCLUSIONS: High risk groups identified in this study should be the priority focus of future public health strategies aimed at reducing listeriosis incidence and mortality.

Listeriosis in fattening pigs caused by poor quality silage - a case report.

BACKGROUND: Listeria (L.) monocytogenes as the causative agent of listeriosis in humans and different animal species, has its reservoir in the environment. It can be found in the gut and faeces of healthy pigs, but under certain circumstances it may cause clinical disease. Fatteners are usually not known to get affected by Listeria-associated septicaemia and enteritis. This case report shows, that L. monocytogenes should be part of the list of differential diagnoses, when fattening pigs suffer from haemorrhagic diarrhoea and septicaemia. CASE PRESENTATION: Here, we report of an episode of fatal listeriosis in fattening pigs in a piglet producing farm in Lower Austria, which was combined with a fattening unit with space for 450 fatteners. The mortality rate resulted in 7.8% among fattening pigs after suffering from clinical symptoms such as anorexia, bloody diarrhoea and increased body temperature. Two fattening pigs with clinical symptoms and maize silage samples were used for further diagnostics. L. monocytogenes were isolated from serosa samples of the pigs and in the corresponding fed maize silage. One animal was positively tested for Brachyspira hyodysenteriae, which may have also been involved in the development of colitis. Immunohistochemically, L. monocytogenes could be detected in high amounts in lymphatic tissue of the gut. Molecular biological characterisation of the L. monocytogenes isolates from pigs and maize silage resulted in an identical DNA-fingerprint assigned to sequence type (ST) 21. Additionally, a high content of deoxynivalenol (3000 parts per billion) was found in maize silage. Therefore, the maize silage produced under inappropriate ensilaging conditions in a silo, was most likely the source of infection. Antimicrobial therapy with amoxicillin led to a fast cure of the remaining affected fatteners. CONCLUSION: To conclude, we were able to show, that L. monocytogenes can cause clinical disease in finishing pigs, which may have been a result of immunosuppression due to high deoxynivalenol exposure. When feeding silage it is important that all ensilaging procedures occur under appropriate anaerobic conditions to guarantee suppression of listerial growth.

Neonatal listeriosis during a countrywide epidemic in South Africa: A tertiary hospital's experience.

BACKGROUND: A countrywide epidemic of Listeria monocytogenes (LM) in South Africa began in the first quarter of 2017, rapidly becoming the world's largest LM outbreak to date. METHODS: We describe the clinical course of neonates with culture-confirmed LM infection admitted to a tertiary neonatal unit at Tygerberg Hospital, Cape Town (1 January 2017 - 31 January 2018). Current epidemic LM cases were compared with a historical cohort of sporadic neonatal LM cases at our institution (2006 - 2016). The global literature on epidemic neonatal LM outbreaks (1 January 1978 - 31 December 2017) was reviewed. RESULTS: Twelve neonates (median gestational age 35 weeks, median birth weight 2 020 g) were treated for confirmed LM bacteraemia in 2017/18, presenting at a median age of 0.5 days. In 5 cases, neurolisteriosis was suspected. Three neonates died (25.0%) v. 8/13 neonatal deaths (61.6%) in the sporadic listeriosis cohort (2006 - 2016) (p=0.075). The institution's neonatal LM infection incidence increased significantly in 2017 from a historical rate of 0.17/1 000 live births to 1.4/1 000 (p<0.001). During the current LM epidemic, the crude neonatal fatality rate exceeded the average calculated global epidemic neonatal LM mortality (3/12 (25.0%) v. 50/290 (17.2%); p=0.448). Possible factors contributing to the high mortality rate in this epidemic LM neonatal cohort may include more virulent disease associated with sequence type 6 and the predominance of early-onset disease. CONCLUSIONS: Epidemic neonatal listeriosis at Tygerberg Hospital was associated with a predominance of bacteraemic, early-onset disease. Listeriosis-associated mortality rates were higher than previously published, but lower than the rate in a historical institutional cohort.

The impact of shelf life on exposure as revealed from quality control data associated with the quargel outbreak.

A cluster of 34 human cases of listeriosis was traced to consumption of contaminated quargel cheese, a sour milk specialty sold in Austria, Germany and Czech Republic. Here, we try to assess how many portions were consumed by the Austrian population at a certain contamination level (CL). In total, 1623 cheese lots were produced during the outbreak period resulting in >3 million portions of cheese delivered to the market. From 650 sets of quality control data provided by the food business operator, we reconstructed the contamination scenario over time and identified 84 lots that were found to be positive. With regard to another sixteen lots, a CL was found ranging from one to 3,84 log10 CFU L. monocytogenes/g, measured in product stored between one to 23 days after production. However the number of storage days at home before consumption is unknown. To resolve this issue, we modelled the theoretical CL of the product if consumed either 20, 30, 40 or 50 days post production. We found that 10 lots (approx. 27,350 portions) would have been contaminated at CLs higher than 3 log10 CFU L. monocytogenes/g if all cheese had been consumed after 20 days of storage. This number shifts to 20 lots (approx. 54,700 portions) after 30 days of storage. If all cheese had been consumed at the end of shelf life (50 days of storage), theoretically 242,5 lots would have exceeded a CL of 6 log10 CFU L. monocytogenes/g. We concluded that the extended shelf life given to the product was a driver of the outbreak scenario. It is stunning to note that so few cases were reported in spite of consumers' massive exposure to L. monocytogenes. We hypothesized that a low pathogenicity of both quargel outbreak clones (QOC1 and QOC2) could have contributed to this discrepancy. Our hypothesis was falsified since both strains QOC1 and QOC2 are fully virulent in an oral infection mouse model, showing even higher pathogenicity than the reference strain EGDe.

Imaging of Human Neurolisteriosis: A Prospective Study of 71 Cases.

Background: Neurolisteriosis ranks among the most severe neurological infections. Its radiological features have not been thoroughly studied. We describe here the neuroradiological features of neurolisteriosis and assess their prognostic value. Methods: Patients with microbiologically proven neurolisteriosis were enrolled from November 2009 to October 2013 in MONALISA study. Magnetic resonance and computed tomography images were studied by 2 independent neuroradiologists. Predictors of 3-month mortality were determined using logistic regression. Results: Seventy-one patients were included; 42 were men (59%). Mean age was 64 years. Sixty patients (85%) reported signs of encephalitis, with clinical brainstem involvement in 16 (23%). Images were abnormal in 87% of cases (62/71). Main neuroradiological images were meningeal enhancement (25/71, 35%), abscess(es), or nodular image(s) evocative of abscess (10/71, 14%), hemorrhages (11/71, 15%), contrast-enhancing ventricles, or hydrocephalus (7/71, 10%). White-matter images (42/71, 59%), dilated Virchow-Robin spaces (22/71, 31%), and cerebral atrophy were also reported (34/71, 48%). Brainstem involvement (meningeal enhancement, abscess) was reported in only 7/71 cases (10%). Three-month survival was lower in patients with hydrocephalus or contrast-enhancing ventricles (1/7 [14%] than without [47/64, 73%], P = .005) and in patients with parenchymal images (abscess[es], nodule[s]\, or white matter images; 25/46 [54%] vs 23/25 without [92%], P = .004). Parenchymal images were associated with lower 3-month survival in the multivariable model (odds ratio 5.60, 95% confidence interval [1.42-29.6], P = .02). Conclusions: Neurolisteriosis presents as a combination of neuroradiological images, none being specific. Radiological signs of rhombencephalitis are uncommon, whereas, unexpectedly, hemorrhagic images are frequent. The negative prognostic value of parenchymal neuroradiological images was evidenced. Clinical Trials Registration: NCT01520597.

Increasing Incidence of Listeriosis and Infection-associated Clinical Outcomes.

BACKGROUND: Listeriosis caused by Listeria monocytogenes has a high case-fatality rate (CFR) of approximately 20% to 30%. An increasing incidence of listeriosis has been reported in many countries recently. We investigated the annual incidence, clinical characteristics, and outcomes of listeriosis at three different hospitals in Korea and evaluated the effects of appropriate empiric antimicrobial treatments on patient outcomes. METHODS: We retrospectively collected the data of all culture-positive cases of human listeriosis from three hospitals of different sizes in Korea during 2006-2016 and calculated the annual number of cases and incidence per 100,000 admissions. RESULTS: A total of 58 patients with L. monocytogenes were included in this study. The incidence of listeriosis was significantly higher in 2013-2016 than in 2006-2012 (RR 3.1; 95% CI 1.79-5.36; P<0.001), mainly because of an increase in patients over 60 years of age (RR 3.69; 95% CI 1.70-8.02; P<0.001). Multivariate analysis showed that healthcare-associated infection (adjusted OR, 12.15; 95% CI, 2.56-86.01; P=0.004) and empirical treatment with first-line antimicrobial agents (adjusted OR, 0.08; 95% CI, 0.00-0.63; P=0.044) were associated with CFR. CONCLUSIONS: Healthcare-associated infections caused by L. monocytogenes are associated with high CFR. Adequate initial empirical treatments could reduce CFR, suggesting that careful consideration of an empirical antimicrobial regimen is warranted for elderly or immunocompromised patients admitted to the hospital.

SNX8 mediates IFNγ-triggered noncanonical signaling pathway and host defense against Listeria monocytogenes.

IFNγ is a cytokine that plays a key role in host defense against intracellular pathogens. In addition to the canonical JAK-STAT1 pathway, IFNγ also activates an IKKß-mediated noncanonical signaling pathway that is essential for induction of a subset of downstream effector genes. The molecular mechanisms and functional significance of this IFNγ-triggered noncanonical pathway remains enigmatic. Here, we identified sorting nexin 8 (SNX8) as an important component of the IFNγ-triggered noncanonical signaling pathway. SNX8-deficiency impaired IFNγ-triggered induction of a subset of downstream genes. Snx8-/- mice infected with Listeria monocytogenes exhibited lower serum cytokine levels and higher bacterial loads in the livers and spleens, resulting in higher lethality. Mechanistically, SNX8 interacted with JAK1 and IKKß and promoted their association. IFNγ induced JAK1-mediated phosphorylation of SNX8 at Tyr95 and Tyr126, which promoted the recruitment of IKKß to the JAK1 complex. SNX8-deficiency impaired IFNγ-induced oligomerization and autophosphorylation of IKKß at Ser177, which is critical for selective induction of downstream genes. Our findings suggest that SNX8 acts as a link for IFNγ-triggered noncanonical signaling pathway, which induces a subset of downstream genes important for host defense against L. monocytogenes infection.