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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.
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Lingling Shao, Chao Qiu, Liheng Zheng, Yang Yang, Xinting Yang, Qingtao Liang, Yun Zhang, Nanying Che, Yu Pang, Hongfei Duan
The aseptic meningitis caused by varicella zoster virus (VZV) reactivation was less described in the literature, most of which were detected by means of polymerase chain reaction. The authors presented 4 adult immunocompetent patients with acute aseptic meningitis with VZV infection diagnosed by next-generation sequencing (NGS).
Four patients were admitted to the hospital with headache and fever between March 2018 and August 2019. The median ages were 37 years (range 22–52 years). The median symptoms onset to clinic time was 3.5 days (range 3–6 days). Two patients had signs of meningeal irritation. Rash occurred after the meningitis symptoms in 1 patient (time from meningitis symptoms to rash, 2 days). No other sign or symptom was reported. The brain Magnetic resonance imaging and electroencephalography were normal in all patients. Cerebrospinal fluid (CSF) samples were obtained at a median of 4 days (range 3–7 days) from the meningitis symptoms onset. Opening pressure of lumbar puncture after admission were high in these cases (median 256 mm H2O; range 165–400 mm H2O). White blood cell counts and protein levels were significantly elevated in CSF samples (median 317 × 10^6/L, range 147–478 × 10^6/L; median 1.41 g/L, range 0.57–1.79 g/L). The cytology of CSF demonstrated a lymphocytic pleocytosis, and most multinuclear cells. The culture of CSF was negative for all 4 cases, while T-cell spot test was positive for 2 cases, who were administrated with anti-tuberculosis treatment for suspicious tuberculous meningitis. NGS of CSF (the Vision Medical Research Institute) detected specific sequences of VZV in the 4 cases within 72 h after admission. The inappropriate treatment were stopped while acyclovir were continued intravenously for 10–14 days. All patients recovered completely.
VZV is an infectious agent that causes aseptic meningitis in immunocompetent adults and could not be accompanied by skin manifestations. The NGS of CSF is a rapid detection for the identification and differentiation of meningitis in patients, which is of great importance for providing the rapid and accurate diagnosis and the targeted antimicrobial therapy for central nervous system infection.
PCRctic is an innovative assay based on 16S rDNA PCR technology that has been designed to detect a single intact bacterium in a specimen of cerebro-spinal fluid (CSF). The assay’s potential for accurate, fast and inexpensive discrimination of bacteria-free CSF makes it an ideal adjunct for confident exclusion of bacterial meningitis in newborn babies where the negative predictive value of bacterial culture is poor. This study aimed to stress-test and optimize PCRctic in the “field conditions” to attain a clinically useful level of specificity.
The specificity of PCRctic was evaluated in CSF obtained from newborn babies investigated for meningitis on a tertiary neonatal unit. Following an interim analysis, the method of skin antisepsis was changed to increase bactericidal effect, and snap-top tubes (Eppendorf™) replaced standard universal containers for collection of CSF to reduce environmental contamination.
The assay’s specificity was 90.5% in CSF collected into the snap-top tubes – up from 60% in CSF in the universal containers. The method of skin antisepsis had no effect on the specificity. All CSF cultures were negative and no clinical cases of neonatal bacterial meningitis occurred during the study.
A simple and inexpensive optimization of CSF collection resulted in a high specificity output. The low prevalence of neonatal bacterial meningitis means that a large multi-centre study will be required to validate the assay’s sensitivity and its negative predictive value.
Asako Doi, Toshikazu Hasuike, Tatsuya Shindo, Hiroaki Nishioka
Donovan J, Cresswell F, Thuong N, et al.
AbstractThe delayed diagnosis of tuberculous meningitis (TBM) leads to poor outcomes, yet the current diagnostic methods for identifying Mycobacterium tuberculosis in cerebrospinal fluid (CSF) are inadequate. The first comparative study of the new GeneXpert MTB/RIF Ultra (Xpert Ultra) for TBM diagnosis suggested increased sensitivity of Xpert Ultra. Two subsequent studies have shown Xpert Ultra has improved sensitivity, but has insufficient negative predictive value to exclude TBM. Collecting and processing large volumes of CSF for mycobacterial testing are important for optimal diagnostic test performance. But clinical, radiological, and laboratory parameters remain essential for TBM diagnosis and empiric therapy is often needed. We therefore caution against the use of Xpert Ultra as a single diagnostic test for TBM; it cannot be used to “rule out” TBM.
Tuula Pelkonen, Suvi Urtti, Elizabete dos Anjos, Ondina Cardoso, Linda de Gouveia, Irmeli Roine, Heikki Peltola, Anne von Gottberg, Moe H. Kyaw
The global burden of bacterial meningitis (BM) remains high even with improving coverage of conjugate vaccines (GBD Meningitis Collaborators, 2018). Although the incidence, aetiology, and outcome vary by age and region (Edmond et al., 2010; GBD Meningitis Collaborators, 2018; Oordt-Speets et al., 2018), the burden is heaviest in Sub-Saharan Africa where the problem is related to poverty (GBD Meningitis Collaborators, 2018). Outside Neisseria meningitidis epidemics, the peak age of BM is in the neonatal period (GBD Meningitis Collaborators, 2018; Heath et al.
Lucía Boix-Palop, Tamara Fernández, Iván Pelegrín, Meritxell Obradors, Kevin García-Roulston, Mariona Xercavins, Dolors García-Somoza, Carmen Ardanuy, Javier Garau, Esther Calbo, Carmen Cabellos
Streptococcus pneumoniae (Sp) is the predominant causative pathogen of community-acquired bacterial meningitis (C-ABM) in adults, causing up to 53% of cases (van de Beek et al., 2016). Pneumococcal meningitis (PM) is associated with a high mortality rate (18-26%) and a high rate of neurological sequelae (20-37%) in surviving patients (van de Beek et al., 2006), (Lucas et al., 2016).
Intracranial infections with Corynebacterium striatum (C. striatum) have been described sporadically in the literature over the last two decades. However, C. striatum meningitis combined with multiple abscesses has not been published before.
In this report, we describe the clinical and imaging findings in a 54-year-old woman with meningitis caused by C. striatum and combined with suspected brain and lung abscesses. This patient who underwent multiple fractures and a recent cut presented with headache and paraphasia. C. striatum was isolated in cerebrospinal fluid and supposedly transmitted from the skin purulent wound through blood. The patient was treated with intravenous vancomycin and had a transient improvement, but died finally. Multiple abscesses, especially in the brain, could be a reason to explain her conditions were deteriorating rapidly.
Note that C. striatum can cause life-threatening infections. Early identification and diagnosis, early administration of antibiotics to which the bacterium is susceptible, and treatment of complications will be beneficial in patients with C. striatum-related infection.
Yueli Zou, Hongzhi Guan, Honglong Wu, Hui Bu, Litian Yan, Yifei Zhu, Junying He
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: firstname.lastname@example.org
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
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.
International Liver Congress (ILC) 2020
27.08.2020 - 29.08.2020
World Sepsis Day
Det 8. videnskabelige nationale møde om infektiøs endokarditis
International Congress for Tropical Medicine and Malaria (ICTMM) 2020
20.09.2020 - 24.09.2020
Meeting of the European Society for Immunodeficiencies (ESID) 2020
14.10.2020 - 17.10.2020
COVID-19 retningslinje (2020)
National handlingsplan for antibiotika til mennesker (2017)
Retningslinjer til sundhedsprofessionelle vedr. håndtering af infektion med zikavirus (2019)
Infections in Patients Colonized with Extended-Spectrum Beta-Lactamase-Producing Enterobacterales – a Retrospective Cohort Study
30.07.2020Clinical Infectious Diseases Advance Access
Effectiveness of Cloth Masks for Protection Against Severe Acute Respiratory Syndrome Coronavirus 2
22.07.2020Emerging Infectious Diseases Journal
Coronavirus Disease among Persons with Sickle Cell Disease, United States, March 20–May 21, 2020
22.07.2020Emerging Infectious Diseases Journal
COVID-19: the worst may be yet to come
First step in a new era for treatment of patients with vitiligo
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