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Rapport og anbefaling vedrørende lumbalpunktur, blodfortyndende behandling og akut bakteriel meningitis. Udarbejdet af en arbejdsgruppe nedsat af Dansk Selskab for Infektionsmedicin vedrørende neuroinfektioner.
Udgiver: Dansk Selskab for Infektionsmedicin 2018
Arbejdsgruppe: Anne-Mette Lebech, Birgitte Rønde Hansen, Christian Brandt, Hans Rudolph von Lüttichau, Jacob Bodilsen, Jannik Helweg-Larsen, Lothar Wiese, Lykke Larsen, Trine Mogensen.
Udgiver: Dansk Selskab for Infektionsmedicin
Arbejdsgruppe: Anne-Mette Lebech, Birgitte Rønde Hansen, Christian Brandt, Hans Rudolf von Lüttichau, Jacob Bodilsen, Lothar Wiese, Lykke Larsen, Trine Mogensen.
Udgiver: Dansk Selskab for Infektionsmedicin
Arbejdsgruppe: Anne-Mette Lebech, Birgitte Rønde Hansen, Christian Brandt, Hans Rudolph von Lüttichau, Jacob Bodilsen, Jannick Helweg-Larsen, Lothar Wiese, Lykke Larsen, Trine Mogensen.
Klinik, diagnostik og behandling af Lyme Borreliose i Danmark.
Forfattergruppen er nedsat af Dansk Selskab for Klinisk Mikrobiologi, Dansk Selskab for Infektionsmedicin og Dansk Neurologisk Selskab.
Tværregional vejledning vedrørende akut bakteriel (purulent) meningitis hos voksne
Vejledning om forebyggelse ved tilfælde af Meningokoksygdom
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Clinicians may be less inclined to consider a diagnosis of cryptococcal meningitis in people without HIV infection or transplant-related immunosuppression. This may lead to a delay in diagnosis particularly if disseminated cryptococcal disease mimics cerebral septic emboli in injection drug use (IDU) leading to a search for endocarditis or other infectious sources. Though, IDU has been described as a potential risk for disseminated cryptococcal disease.
We present two cases of cryptococcal meningitis in IDU without HIV or other obvious immune deficits. Both patients presented with at least 2 weeks of headache and blurred vision. They developed central nervous system (CNS) vasculitis, one of which mimicked septic cerebral emboli, but both resulted with poor neurologic outcomes.
IDU likely induces an underappreciated immune deficit and is a risk factor for developing cryptococcal meningitis. This diagnosis, which can mimic cerebral septic emboli through involvement of a CNS vasculitis, should be considered in the setting of IDU.
Paul Le Turnier, Matthieu Gregoire, Guillaume Deslandes, Karim Lakhal, Colin Deschanvres, Raphael Lecomte, Jean-Philippe Talarmin, Vincent Dubée, Ronan Bellouard, David Boutoille, Anne-Gaëlle Leroy, Benjamin Jean Gaborit, NAMAP study group Nantes Anti-Microbial Agent Pk/PD
The main objective of the study was to assess the meningeal penetration of cefazolin and cloxacillin in patients treated for methicillin-susceptible staphylococcal meningitis.
Liping Yan, Wenwen Sun, Zhenhui Lu, Lin Fan
Cerebrospinal fluid (CSF) analyses are recommended in patients with meningitis and/or encephalitis, but evidence regarding its diagnostic yield is low. We aimed to determine predictors of infectious pathogens in the CSF of adult patients presenting with meningitis, and/or encephalitis.
Consecutive patients with meningitis and/or encephalitis form 2011–17 at a Swiss academic medical care center were included in this cross-sectional study. Clinical, neuroradiologic, and laboratory data were collected as exposure variables. Infectious meningitis and/or encephalitis were defined as the composite outcome.
For diagnosis of bacterial meningitis the recommendations of the European Society of Clinical Microbiology and Infectious Diseases were followed. Viral meningitis was diagnosed by detection of viral ribonucleic or deoxyribonucleic acid in the CSF. Infectious encephalitis was defined according to the International Encephalitis Consortium (IEC). Meningoencephalitis was diagnosed if the criteria for meningitis and encephalitis were fulfilled. Multinomial logistic regression was performed to identify predictors of the composite outcome. To quantify discriminative power, the c statistic analogous the area under the receiver-operating curve (AUROC) was calculated. An AUROC between 0.7–0.8 was defined as “good”, 08–0.9 as “excellent”, and > 0.9 as “outstanding”. Calibration was defined as “good” if the goodness of fit tests revealed insignificant p-values.
Among 372 patients, infections were diagnosed in 42.7% presenting as meningitis (51%), encephalitis (32%), and meningoencephalitis (17%). Most frequent infectious pathogens were Streptococcus pneumoniae, Varicella zoster, and Herpes simplex 1&2. While in multivariable analysis lactate concentrations and decreased glucose ratios were the only independent predictors of bacterial infection (AUROCs 0.780, 0.870, and 0.834 respectively), increased CSF mononuclear cells were the only predictors of viral infections (AUROC 0.669). All predictors revealed good calibration.
Prior to microbiologic workup, CSF data may guide clinicians when infection is suspected while other laboratory and neuroradiologic characteristics seem less useful. While increased CSF lactate and decreased glucose ratio are is the most reliable predictors of bacterial infections in patients with meningitis and/or encephalitis, only mononuclear cell counts predicted viral infections.
ClinicalTrials.gov identifier NCT03856528. Registered on February 26th 2019.
Donovan, Joseph; Thwaites, Guy E.; Huynh, Julie
Purpose of review
Tuberculous meningitis (TBM) is associated with significant mortality and morbidity yet is difficult to diagnose and treat. We reviewed original research published in the last 2 years, since 1 January 2018, which we considered to have a major impact in advancing diagnosis, treatment and understanding of the pathophysiology of TBM meningitis in children and adults.
Studies have sought to identify a high sensitivity diagnostic test for TBM, with new data on modified Ziehl--Neelsen staining, urinary and cerebrospinal fluid (CSF) lipoarabinomannan and GeneXpert Ultra. Recent studies on CSF biomarkers provide a better understanding of the detrimental inflammatory cascade and neuromarkers of brain damage and suggest potential for novel host-directed therapy. Tryptophan metabolism appears to affect outcome and requires further study. Increased clinical trials activity in TBM focuses on optimizing antituberculosis drug regimens and adjuvant therapy; however, there are few planned paediatric trials.
Tuberculous meningitis still kills or disables around half of sufferers. Although some progress has been made, there remains a need for more sensitive diagnostic tests, better drug therapy, improved management of complications and understanding of host-directed therapy if outcomes are to improve.
Correspondence to Joseph Donovan, Oxford University Clinical Research Unit, Centre for Tropical Medicine, Ho Chi Minh City, Vietnam. Tel: +84839239207; e-mail: email@example.com
This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
Schwendinger M, Thiry G, De Vos B, et al.
AbstractBackgroundA vaccine (HB-101) consisting of 2 nonreplicating lymphocytic choriomeningitis virus (LCMV) vectors expressing the human cytomegalovirus antigens glycoprotein B (gB) and the 65-kD phosphoprotein (pp65), respectively, is in development to prevent cytomegalovirus infection.MethodsHB-101 was tested in cytomegalovirus-naive, healthy adults in a randomized, double-blind, placebo-controlled, dose-escalation Phase I trial. Fifty-four subjects received low, medium, or high dose of HB-101 or placebo by intramuscular administration at Month 0, 1, and 3. Safety and immunogenicity were the respective primary and secondary endpoints. Subjects were followed for 12 months after the initial immunization.ResultsVaccination was associated with transient mild to moderate adverse events. HB-101 administration induced dose-dependent gB- and pp65-specific cellular responses, dominated by pp65-specific CD8 T cells, a high fraction of which were polyfunctional. Two administrations were sufficient to elicit dose-dependent gB-binding and cytomegalovirus-neutralizing antibodies (Abs). Cytomegalovirus-specific immune responses were boosted after each administration. Only 1 of 42 vaccine recipients mounted a transient LCMV vector-neutralizing Ab response.ConclusionsHB-101 was well tolerated and induced cytomegalovirus-specific polyfunctional CD8 T-cell and neutralizing Ab responses in the majority of subjects. Lack of vector-neutralizing Ab responses should facilitate booster vaccinations. These results justify further clinical evaluation of this vaccine candidate.
Studies on bacterial meningitis in diabetics patients versus non-diabetics are scarce. In patients with diabetes, bacterial meningitis may have a different presentation, etiology and course. We analyzed and compared the characteristics and outcome of spontaneous BM in adult patients with and without diabetes mellitus (DM).
We performed a single-center, prospective observational cohort study, conducted between 1982 and 2017, in a tertiary university hospital in Barcelona (Spain). The primary outcome measure was in-hospital mortality.
We evaluated 715 episodes of bacterial meningitis; 106 patients (15%) had diabetes mellitus. Patients with diabetes were older (median 67 [IQR 17] vs 49 [IQR 40] years, p
Bacterial meningitis remains a major threat for the population of the meningitis belt. Between 2004 and 2009, in the countries of this belt, more than 200,000 people were infected with a 10% mortality rate. However, for almost 20 years, important meningitis epidemics are also reported outside this belt. Research is still very poorly developed in this part of the word like in the Democratic Republic of Congo (DRC), which experiences recurrent epidemics. This article describes for the first time the spatio-temporal patterns of meningitis cases and epidemics in DRC, in order to provide new insights for surveillance and control measures.
Based on weekly suspected cases of meningitis (2000–2012), we used time-series analyses to explore the spatio-temporal dynamics of the disease. We also used both geographic information systems and geostatistics to identify spatial clusters of cases. Both using conventional statistics and the Cleveland’s algorithm for decomposition into general trend, seasonal and residuals, we searched for the existence of seasonality.
We observed a low rate of biological confirmation of cases (11%) using soluble antigens search, culture and PCR. The main strains found are Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis (A and C) serogroups. We identified 8 distinct spatial clusters, located in the northeastern and southeastern part of DRC, and in the capital city province, Kinshasa. A low seasonal trend was observed with higher incidence and attack rate of meningitis during the dry season, with a high heterogeneity in seasonal patterns occurring across the different districts and regions of DRC.
Despite challenges related to completeness of data reporting, meningitis dynamics shows weak seasonality in DRC. This tends to suggest that climatic, environmental factors might be less preponderant in shaping seasonal patterns in central Africa. The characterization of 8 distinct clusters of meningitis could be used for a better sentinel meningitis surveillance and optimization of vaccine strategy in DRC. Improving biological monitoring of suspected cases should be a priority for future eco-epidemiological studies to better understand the emergence and spread of meningitis pathogens, and the potential ecological, environmental drivers of this disease.
An ambitious and far-sighted plan focusing for the first time on a universal reduction of the burden of disease caused by meningitis is scheduled for discussion at this year's World Health Assembly in May. The proposal—titled Defeating Meningitis by 2030—highlights bacterial meningitis, for which progress in the reduction of both mortality and morbidity has substantially lagged behind that made with other vaccine-preventable diseases. It calls for improvements in five areas: prevention and epidemic control; diagnosis and treatment; surveillance; support and care for patients affected by the sequelae of an infection; and engagement and advocacy.
Savonius O, Rugemalira E, Roine I, et al.
AbstractBackgroundIn our previous study in Luanda, Angola, initial continuous β-lactam infusion for 24 hours combined with oral acetaminophen for 48 hours showed promising results as a new treatment for childhood bacterial meningitis. We investigated whether extending this treatment regimen to 4 days would improve the outcomes further.MethodsWe conducted a randomized, double-blind, parallel-group study at the same hospital in Luanda. Children aged 2 months to 15 years presenting to hospital with symptoms and signs of bacterial meningitis were randomized to receive, for the first 4 days, a continuous infusion of cefotaxime (250mg/kg/day) with simultaneous oral acetaminophen (first dose 30 mg/kg, then 20 mg/kg every 6 hours), or cefotaxime conventionally as boluses (62.5 mg/kg, 4 times per day) with placebo orally. All children received also glycerol orally. The primary outcome was mortality by day 7.ResultsIn all, 375 patients were included in the study between January 22, 2012 and January 21, 2017. As two children succumbed before treatment initiation, 187 vs. 186 participants remained in the intervention and control groups, respectively. On day 7, 61/187 (32.6%) children in the intervention group versus 64/186 (34.4%) in the control group had died (risk ratio 0.95, 95% confidence interval [95% CI] 0.71 –1.26; absolute risk difference 1.8%, 95% CI -7.8 – 11.4). At discharge from hospital, the corresponding numbers were 71/187 (38.0%) and 75/186 (40.3%).ConclusionsProlonged continuous β-lactam infusion combined with oral acetaminophen did not improve the gloomy outcomes of childhood bacterial meningitis in Angola.
Takeshi Moriguchi, Norikazu Harii, Junko Goto, Daiki Harada, Hisanori Sugawara, Junichi Takamino, Masateru Ueno, Hiroki Sakata, Kengo Kondo, Natsuhiko Myose, Atsuhito Nakao, Masayuki Takeda, Hirotaka Haro, Osamu Inoue, Katsue Suzuki-Inoue, Kayo Kubokawa, Shinji Ogihara, Tomoyuki Sasaki, Hiroyuki Kinouchi, Hiroyuki Kojin, Masami Ito, Hiroshi Onishi, Tatsuya Shimizu, Yu Sasaki, Nobuyuki Enomoto, Hiroshi Ishihara, Shiomi Furuya, Tomoko Yamamoto, Shinji Shimada
Haiyan Yang, Fei Yin, Ting Xiao, Siyi Gan, Zou Pan, Jing Peng, Liwen Wu
Cryptococcus meningitis (CM) is a subacute or chronic deep fungal infection of central nervous system, which is the most severe clinical manifestation caused by cryptococcus (Mpoza et al., 2019). The epidemiological data of the foreign countries show that the acquired immunodeficiency syndrome (AIDS) - related CM is more common (Bennett et al., 1979; Dismukes et al., 1987; Pappas et al., 2001; Mirza et al., 2003; Dromer et al., 2007 ), but the epidemiological data in China show that 50-77% of patients with CM have normal immune function (Lu et al., 1999; Kombila et al., 2016; Yao et al., 2005; Lui et al., 2006; Zhu et al., 2010; ), which suggested that Chinese CM patients have a certain particularity.
Esther Vaugon, Patricia S. Fontela, Jesse Papenburg
Central nervous system infections are associated with significant morbidity and mortality. Prompt diagnosis and treatment are crucial for recovery without major sequelae. In October 2015, the U.S. Food and Drug Administration (FDA) approved the FilmArray meningitis/encephalitis (ME) Panel (Biofire Diagnostics, Salt Lake City, UT) the first multiplex PCR panel for diagnosis of infections in cerebrospinal fluid. The assay tests for 14 viral, bacterial and fungal pathogens, provides results within 60 minutes, and is becoming more commonly used in clinical laboratories.
Gareth Hughes, Chris A. Green, Duncan Street, Yasmine Maurice, John Henderson, Andrew Woodhouse, David Nicholl and James E. Scriven
Human infection with the trematode Fasciola occurs with a worldwide prevalence of up to 17 million. Sheep and cattle are the normal host. Infection typically results in hepatobiliary disease, but extrahepatic manifestations are occasionally reported. Here, we present the case of a previously healthy 31-year-old Kurdish woman, admitted to hospital with a subarachnoid hemorrhage, eosinophilic meningitis, and lung and liver disease. A diagnosis of Fasciola infection was made based on strongly positive serology in blood and cerebrospinal fluid. The patient improved following treatment with triclabendazole and prednisolone.
Death from bacterial meningitis is rarely attributed to the actual event causing death.
The present study therefore categorized and characterized the cause and time of death due to bacterial meningitis.
In a cohort of patients > 15 years of age with community acquired bacterial meningitis the medical records were reviewed, and a clinical cause of death categorized into six main categories: 1) CNS complications, 2) Systemic complications, 3) Combination of systemic and CNS complications, 4) Sudden death, 5) Withdrawal of care, or 6) Unknown.
We identified 358 patients of which 84 (23%) died in-hospital. Causes of death were ascribed to CNS complications in 43%, Systemic complications in 39%, Combined CNS and systemic complications in 4%, Sudden death in 7% and withdrawal of care in 5%. Brain herniation, circulatory failure, intractable seizures and other brain injury were the most common specific causes of death within 14 days from admission (55%).
Fatal complications due to the primary infection – meningitis - is most common within 14 days of admission. The diversity of complications causing death in meningitis suggest that determining the clinical cause of death is essential to the evaluation of novel treatment strategies.
T. Goyal and I. Ali
Infectious meningitis is a serious disease and patient outcome relies on fast and reliable diagnostics. A syndromic panel testing approach like the FilmArray ME can accelerate diagnosis and therefore decrease the time to pathogen specific therapy. Yet, its clinical utility is controversial, mainly because of a remaining uncertainty in correct interpretation of results, limited data on its performance on clinical specimens and its relatively high costs. The aim of this study was to analyze clinical performance of the assay in a real life setting at a tertiary university hospital using a pragmatic and simple sample selection strategy to reduce the overall cost burden.
Over a period of 18 months we received 4623 CSF samples (2338 hospitalizations, 1601 individuals). FilmArray ME analysis was restricted to CSF-samples with a high pretest probability of infectious meningitis, e.g. positive Gram-stain, samples in which leukocytes and/or bacteria were evident or urgent suspicion of infection was communicated by clinicians. N = 171 samples matched to our risk criteria and were subjected to FilmArray ME analysis. Those samples were also analyzed by reference methods: culture only (n = 45), PCR only (n = 20) or both methods (n = 106).
56/171 (32.75%) were FilmArray ME positive. Bacterial pathogens were detected in 30/56 (53.57%), viral pathogens were detected in 27/56 (48.21%) and yeast DNA was detected in 1/56 (1.79%) of positive samples. Double detection occurred in 2/56 samples. In 52/56 (92.86%) FilmArray ME positive samples, results could be confirmed by the reference assays (sensitivity = 96.30%, specificity =96.58%).
The FilmArray ME assay is a fast and reliable diagnostic tool for the management of infectious meningitis and can easily be implemented in routine diagnostic workflows. However, correlation of test results and underlying clinical symptoms requires experienced users and the awareness of potentially false negative or false positive results. Moreover, considering the need for antimicrobial susceptibility testing, the use of molecular tests as a stand-alone diagnostic cannot be recommended.
Hélène Mascitti, Ruxandra Calin, Aurélien Dinh, Sabrina Makhloufi, Benjamin Davido
Toscana virus (TOSV) belongs to the arthropod-borne virus. It is a common cause of meningitis or meningo-encephalitis in Mediterranean area, typically reported in Southern Europe (Cusi et al., 2010) (see Fig. 1). In the literature, numerous TOSV meningitis have been described, including complicated neurological disorders (Sanbonmatsu-Gámez et al., 2009; Baldelli et al., 2004). Only rare publications reported extra-meningeal involvement (Charrel et al., 2005), particularly two cases which reported a testicle pain (Baldelli et al., 2004; Zanelli et al., 2013).
Xiaosong Song, Lan Wen, Maolin Li, Xinyuan Yu, Lijun Wang, Kunyi Li
This study aimed to determine the characteristics and risk factors of adult new-onset seizure patients with tuberculous meningitis (TBM) during long-term follow-up.
Invasive infections caused by Capnocytophaga canimorsus are rare. Immunocompromised patients, who report being bitten by or having a close contact with an animal, represent a high-risk group for this infection. There are only few dozens of infections by this bacteria manifesting as purulent meningitis reported worldwide. The reported case is a first reported case of purulent meningitis caused by by Capnocytophaga canimorsus in Czech Republic with only a limited risk factor history.
The patient, a 74 years old man, was referred to the infectious diseases department of a teaching hospital with clear signs of developing purulent meningitis. His anamnestic data did not show any unusual findings. He was treated for compensated diabetes mellitus type II. The blood cultures were negative and the etiological agent did not grow from the cerebrospinal fluid (CSF) on common media. Eventually, it was identified by detecting pan-bacterial DNA and DNA sequencing. Subsequently, the pathogen was confirmed by anaerobic cultivation from CSF. Only after then the patient recalled being bitten by his German shepherd puppy during play. The patient was successfully treated intravenously by ceftriaxone.
Purulent meningitis caused by Capnocytophaga spp. is a rare disease, but it needs to be considered in patients at risk with pre-existing conditions, who report close contact with or being bitten by an animal. It is important to test for this microbe in cases with negative microbiological results for the more common agents.
To estimate long term survival, health, and educational/social functioning in patients with Lyme neuroborreliosis compared with the general population.
To monitor epidemiological trends of infectious meningitis (bacterial and viral) and encephalitis in Denmark.
To examine clinical characteristics and outcome of patients with late diagnosis of community-acquired bacterial meningitis (CABM).
The purpose of this review is to give an overview of viral meningitis and then focus in on some of the areas of uncertainty in diagnostics, treatment and outcome.
The treatment of persistent symptoms attributed to Lyme disease remains controversial. We assessed whether longer-term antibiotic treatment of persistent symptoms attributed to Lyme disease leads to better outcomes than does shorter-term treatment.
To describe the clinical manifestations, cerebrospinal fluid (CSF) characteristics, imaging studies and prognostic factors of adverse clinical outcomes (ACO) among adults with herpes simplex virus (HSV) or varicella zoster virus (VZV) CNS infections.
Encephalitis continues to result in substantial morbidity and mortality worldwide. Advances in diagnosis and management have been limited, in part, by a lack of consensus on case definitions, standardized diagnostic approaches, and priorities for research.
Lyme borreliosis (Lyme disease) is caused by spirochaetes of the Borrelia burgdorferi sensu lato species complex, which are transmitted by ticks. The most common clinical manifestation is erythema migrans, which eventually resolves, even without antibiotic treatment. However, the infecting pathogen can spread to other tissues and organs, causing more severe manifestations that can involve a patient's skin, nervous system, joints, or heart. The incidence of this disease is increasing in many countries. Laboratory evidence of infection, mainly serology, is essential for diagnosis, except in the case of typical erythema migrans. Diagnosed cases are usually treated with antibiotics for 2-4 weeks and most patients make an uneventful recovery. No convincing evidence exists to support the use of antibiotics for longer than 4 weeks, or for the persistence of spirochaetes in adequately treated patients. Prevention is mainly accomplished by protecting against tick bites. There is no vaccine available for human beings.
Lyme borreliosis, caused by spirochaetes of the Borrelia burgdorferi genospecies complex, is the most commonly reported tick-borne infection in Europe and North America. The non-specific nature of many of its clinical manifestations presents a diagnostic challenge and concise case definitions are essential for its satisfactory management. Lyme borreliosis is very similar in Europe and North America but the greater variety of genospecies in Europe leads to some important differences in clinical presentation. These new case definitions for European Lyme borreliosis emphasise recognition of clinical manifestations supported by relevant laboratory criteria and may be used in a clinical setting and also for epidemiological investigations.
Mortality and morbidity rates are high among adults with acute bacterial meningitis, especially those with pneumococcal meningitis. In studies of bacterial meningitis in animals, adjuvant treatment with corticosteroids has beneficial effects.
Lyme disease is the most common vector-borne infection in some temperate regions of the Northern Hemisphere. However, for most areas of endemic disease reliable epidemiologic data are sparse.
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