Klik på linket nedenfor, tryk derefter Ctrl + C eller højreklik for at kopiere det.
Nedenfor kan du finde abstracts fra de nyeste artikler indenfor udvalgte internationale tidsskrifter med infektionsmedicinsk relevans. Du kan under "Yderligere søgekriterier" vælge tidsskrifter, hvor langt tilbage i tiden og rækkefølge.
Vælg eventuelt et eller flere søgeord til at afgrænse søgningen. Match, hvis mindst 1 ord er fundet. Benyt semikolon mellem hvert ord.
Vælg et eller flere tidsskrifter fra listen.
Alle | Ingen
Vælg hvor mange dage tilbage i tiden, der skal vælges artikler fra.
Vælg, hvordan resultaterne skal sorteres.
Søgeord (%s) valgt. Opdateret for 8 timer siden.59 emner vises.
Nocardiosis is an uncommon disease caused by aerobic gram-positive bacteria Nocardia spp. Although it is usually an opportunistic infection affecting immunocompromised patients, even one third of cases occur in immunocompetent persons. The aim of the study was to describe the course of chronic meningitis due to Nocardia infection.
A 52-year-old patient, chalk miner, suffered from a chronic meningitis caused by an extremely rare pathogen. The patient’s history was complicated and diagnostic process covered multiple examinations and consultations. Initially Kocuria rosea was cultured, yet after molecular examination the result was verified to Nocardia farcinica. Targeted antibiotic treatment was implemented, which resulted in gradual improvement of patients condition. A full recovery was achieved after one year antibiotic therapy.
Nocardia farcinica is an uncommon but possible cause of chronic meningitis.
In the case of a chronic meningitis of unknown origin multiple cerebrospinal fluid cultures should be performed as the identification of pathogen may be crucial for patient’s recovery.
In case of unusual culture, such as Kocuria spp. PCR should be performed.
Group B Streptococcal (GBS) infections in the United States are a leading cause of meningitis and sepsis in newborns. The CDC therefore recommends GBS screening for all pregnant women at 35–37 weeks of gestation and administration of intrapartum prophylaxis (in those that tested positive) as an effective means of controlling disease transmission. Several FDA approved molecular diagnostic tests are available for rapid and accurate detection of GBS in antepartum women.
In this study, we report a clinical comparison of the Xpert GBS LB assay and a novel FDA-cleared test, Revogene GBS LB assay. A total of 250 vaginal-rectal swabs from women undergoing prenatal screening were submitted to the University of Wisconsin’s clinical microbiology laboratory for GBS testing.
We found 96.8% of samples were concordant between the two tests, while 3.2% were discordant with a positive percent agreement of 98.0% and a negative percent agreement of 96.5% between the Revogene GBS LB assay and the GeneXpert GBS LB assay.
Overall, we report that both assays perform well for the detection of GBS colonization in pregnant women.
Sarah Tubiana, Emmanuelle Varon, Charlotte Biron, Marie-Cecile Ploy, Bruno Mourvillier, Muhamed-Kheir Taha, Mathieu Revest, Claire Poyart, Guillaume Martin-Blondel, Marc Lecuit, Eric Cua, Blandine Pasquet, Marie Preau, Bruno Hoen, Xavier Duval, the COMBAT study group, Principal investigator, Steering Committee, Scientific committee: steering committee and the following members, COMBAT Clinical Centers, Coordination and statistical analyses (Clinical trial unit, Hôpitaux Universitaires Paris Nord Val de Sein
To identify factors associated with unfavorable in-hospital outcome (death or disability) in adults with community-acquired bacterial meningitis (CABM).
Pullen M, Hullsiek K, Rhein J, et al.
AbstractBackgroundIn cryptococcal meningitis phase two clinical trials, early fungicidal activity (EFA) of Cryptococcus clearance from cerebrospinal fluid (CSF) is used as a surrogate endpoint for all-cause mortality. The FDA allows for using surrogate endpoints for accelerated regulatory approval, but EFA as a surrogate endpoint requires further validation. We examined the relationship between rate of CSF Cryptococcus clearance (EFA) and mortality through 18-weeks.MethodsWe pooled individual-level CSF data from three sequential cryptococcal meningitis clinical trials conducted during 2010-2017. All 738 subjects received amphotericin + fluconazole induction therapy and had serial quantitative CSF cultures. The log10-transformed colony forming units (CFUs) per mL CSF were analyzed by general linear regression versus day of culture over the first 10 days.ResultsMortality through 18-weeks was 37% for EFA >=0.60 (n=170), 36% for 0.40-0.59 (n=182), 39% for 0.30-0.39 (n=112), 35% for 0.20-0.29 (n=87), and 50% for those with EFA
Angharad G Davis, Robert J Wilkinson
Tuberculous meningitis is the most serious manifestation of tuberculosis, with mortality in approximately 50% of HIV co-infected people.1 A major factor contributing to the poor outcome of tuberculous meningitis is delayed diagnosis due to a lack of rapid, accurate diagnostic tests. Until recently, these tests were restricted to smear microscopy of cerebrospinal fluid (CSF) and microbiological culture. The former tends operationally to be of low sensitivity and the latter often renders a result too late to be clinically meaningful.
Joseph Donovan, Do Dang Anh Thu, Nguyen Hoan Phu, Vu Thi Mong Dung, Tran Phu Quang, Ho Dang Trung Nghia, Pham Kieu Nguyet Oanh, Tran Bao Nhu, Nguyen Van Vinh Chau, Vu Thi Ngoc Ha, Vu Thi Ty Hang, Dong Huu Khanh Trinh, Ronald B Geskus, Le Van Tan, Nguyen Thuy Thuong Thuong, Guy E Thwaites
Xpert Ultra was not statistically superior to Xpert for the diagnosis of tuberculous meningitis in HIV-uninfected and HIV-infected adults. A negative Xpert Ultra or Xpert test does not rule out tuberculous meningitis. New diagnostic strategies are urgently required.
Fiona V Cresswell, Lillian Tugume, Nathan C Bahr, Richard Kwizera, Ananta S Bangdiwala, Abdu K Musubire, Morris Rutakingirwa, Enock Kagimu, Edwin Nuwagira, Edward Mpoza, Joshua Rhein, Darlisha A Williams, Conrad Muzoora, Daniel Grint, Alison M Elliott, David B Meya, David R Boulware, ASTRO-CM team
Xpert Ultra detected tuberculous meningitis with higher sensitivity than Xpert and MGIT culture in this HIV-positive population. However, with a negative predictive value of 93%, Xpert Ultra cannot be used as a rule-out test. Clinical judgment and novel highly sensitive point-of-care tests are still required.
Meningitis is a very rare atypical presenting feature of anti-NMDA receptor encephalitis. In our case report, we describe an unusual clinical presentation of anti-NMDA receptor encephalitis with a biphasic pattern of meningitis followed by encephalitis and discuss potential mechanisms underlying this presentation. We aim to widen the differential diagnosis to be considered in a patient presenting with clinical meningitis and pyrexia.
This is a case of a 33-year old Caucasian woman who initially presented with a lymphocytic meningitis attributed to a viral infection. She subsequently developed fluctuating consciousness, agitation, visual hallucinations, dyskinetic movements, a generalized tonic-clonic seizure, and autonomic instability. Investigations revealed a diagnosis of anti-NMDA receptor encephalitis secondary to a previously unidentified ovarian teratoma. She made an excellent recovery with immunotherapy and removal of the teratoma.
Clinicians should consider autoimmune encephalitides in individuals with meningitis, particularly where extensive investigations fail to identify a causative pathogen and there is rapid development of an encephalitic phenotype.
A well described case of the emergence of drug resistance in Streptococcus pneumoniae meningitis during therapy with ceftriaxone monotherapy with a low bactericidal concentration in the cerebrospinal fluid. Adherence to international guidelines could possibly prevented the emergence of this resistant isolate and the adverse outcome.
Bacillus cereus sometimes causes central nervous system infection, especially in compromised hosts. In cases of meningitis arising during neutropenia, CSF abnormalities tend to be subtle and can be easily overlooked, and mortality rate is high. We report a survived case of B. cereus meningitis/brain abscess in severe neutropenia, presenting as immune reconstitution syndrome.
A 54-year-old Japanese female with acute myelogenous leukemia developed B. cereus bacteremia and meningitis during consolidation chemotherapy. At the onset, she presented with mild meningism. She had marked leukocytopenia (WBC
Central nervous system (CNS) tuberculomas are a challenging manifestation of extrapulmonary tuberculosis often leading to neurological complications and post-treatment sequelae. The role of adjunctive corticosteroid treatment is not fully understood. Most guidelines on management of tuberculosis do not distinguish between tuberculous meningitis and CNS tuberculomas in terms of corticosteroid therapy.
We describe five patients with CNS tuberculomas who required intensified dexamethasone treatment for several months, in two cases up to 18 months.
These patients were initially treated with the standard four-drug tuberculosis regimen and adjuvant dexamethasone. Neurological symptoms improved rapidly. However, multiple attempts to reduce or discontinue corticosteroids according to guideline recommendations led to clinical deterioration with generalized seizures or new CNS lesions. Thus, duration of adjunctive corticosteroid therapy was extended eventually leading to clinical cure and resolution of lesions.
In contrast to tuberculous meningitis, the treatment for CNS tuberculomas appears to require a prolonged administration of corticosteroids. These findings need to be verified in controlled clinical studies.
Nazli Ayhan, Remi N. Charrel
Toscana virus is an arbovirus transmitted by sand flies within the Mediterranean area where it can cause febrile illness and neuroinvasive infections during the seasonal circulation period of the vector. Although it is an important cause of meningitis and encephalitis, it remains a neglected virus with limited published data as demonstrated by less than 250 peer-reviewed articles since the 1970's.
P. Vetter, M. Schibler, J.L. Herrmann, D. Boutolleau
Cerebrospinal fluid (CSF) testing is a key component for the diagnosis of central nervous system (CNS) infections. Current meningitis and encephalitis management guidelines agree on the need for CSF molecular testing in combination with other direct and indirect biological testing, both in CSF and blood. Multiplex molecular tests have been developed to reduce turnaround times and facilitate the diagnostic approach.
Okurut, S., Meya, D. B., Bwanga, F., Olobo, J., Eller, M. A., Cham-Jallow, F., Bohjanen, P. R., Pratap, H., Palmer, B. E., Hullsiek, K. H., Manabe, Y. C., Boulware, D. R., Janoff, E. N.
Background: Activated B cells modulate infection by differentiating into pathogen-specific antibody-producing effector plasmablasts/plasma cells, memory cells and immune regulatory B cells. In this context, the B cell phenotypes that infiltrate the central nervous system during HIV and cryptococcal meningitis co-infection are ill defined.Methods: We characterized clinical parameters, mortality and B cell phenotypes in blood and CSF by flow cytometry in HIV-infected adults with cryptococcal (n=31), and non-cryptococcal meningitis (n=12), and heathy control subjects with neither infection (n=10).Results: Activation of circulating B cells (CD21low) was significantly higher in blood of subjects with HIV infection compared with healthy controls, and greater yet in matched CSF B cells (p
Auger, J.-P., Rivest, S., Benoit-Biancamano, M.-O., Segura, M., Gottschalk, M.
Streptococcus suis is an important porcine bacterial pathogen and zoonotic agent responsible for sudden death, septic shock and meningitis. These pathologies are a consequence of elevated bacterial replication leading to exacerbated and uncontrolled inflammation, a hallmark of the S. suis systemic and central nervous system (CNS) infections. Monocytes and neutrophils are immune cells involved in various functions, including pro-inflammatory mediator production. Moreover, monocytes are composed of two main subsets: shorter-lived inflammatory monocytes and longer-lived patrolling monocytes. However, regardless of their presence in blood and that S. suis-induced meningitis is characterized by infiltration of monocytes and neutrophils into the CNS, their role during the S. suis systemic and CNS diseases remains unknown. Consequently, we hypothesized that monocytes and neutrophils participate in S. suis infection via bacterial clearance and inflammation. Results demonstrated that inflammatory monocytes and neutrophils regulate S. suis-induced systemic disease via their role in inflammation required for bacterial burden control. In the CNS, inflammatory monocytes contributed to exacerbation of S. suis-induced local inflammation while neutrophils participated in bacterial burden control. However, development of clinical CNS disease was independent of both cell types, indicating that resident immune cells are mostly responsible for S. suis-induced CNS inflammation and clinical disease and that inflammatory monocyte and neutrophil infiltration is a consequence of the induced inflammation. By contrast, implication of patrolling monocytes was minimal throughout the S. suis infection. Consequently, this study demonstrates that while inflammatory monocytes and neutrophils modulate S. suis-induced systemic inflammation and disease, they are not critical for CNS disease development.
Rungelrath, V., Öhlmann, S., Alber, G., Schrödl, W., von Köckritz-Blickwede, M., de Buhr, N., Martens, A., Baums, C. G., Schütze, N.
Bacteremia is a hallmark of invasive Streptococcus suis (S. suis) infections of pigs often leading to septicemia, meningitis or arthritis. An important defense mechanism of neutrophils is the generation of reactive oxygen species (ROS). In this study, we report high levels of ROS production by blood granulocytes post intravenous infection of a pig with high levels of S. suis-specific antibodies and comparatively low levels of bacteremia. This prompted us to investigate the working hypothesis that immunoglobulin-mediated oxidative burst contributes to killing of S. suis in porcine blood. Several S. suis strains representing serotypes 2, 7 and 9 proofed to be highly susceptible to the oxidative burst intermediate hydrogen peroxide, already at concentrations of 0.001%. The induction of ROS in granulocytes in ex vivo infected reconstituted blood showed association with pathogen-specific antibody levels. Importantly, inhibition of ROS production by the NADPH oxidase inhibitor apocynin led to significantly increased bacterial survival in the presence of high specific antibody levels. The oxidative burst rate of granulocytes partially depended on complement activation as shown by specific inhibition. Furthermore, treatment of an IgG-depleted serum with a specific IgM protease or heat to inactivate complement resulted in a more than 3-fold decreased oxidative burst activity and increased bacterial survival in reconstituted porcine blood in accordance with an IgM-complement-oxidative burst axis. In conclusion, this study highlights an important control mechanism of S. suis bacteremia in the natural host: the induction of ROS in blood granulocytes via specific immunoglobulins such as IgM.
Rhoden, E., Ng, T. F. F., Campagnoli, R., Nix, W. A., Konopka-Anstadt, J., Selvarangan, R., Briesach, L., Oberste, M. S., Weldon, W. C.
Viruses in species Parechovirus A (Picornaviridae) are associated with a wide variety of clinical manifestations. Parechovirus A3 (PeV-A3) is known to cause sepsis-like illness, meningitis, and encephalitis in infants and young children. To date, no specific therapies are available to treat PeV-A3-infected children. We had previously identified two FDA-cleared antifungal drugs, itraconazole (ITC) and posaconazole (POS) with potent and specific antiviral activity against PeV-A3. Time-of-addition and synchronized infection assays revealed that POS targets an early stage of the PeV-A3 life cycle. POS exerts an antiviral effect, evidenced by a reduction in viral titer following the addition of POS to Vero-P cells before infection, coaddition of POS and PeV-A3 to Vero-P cells, incubation of POS and PeV-A3 prior to Vero-P infection, and at attachment. POS exerts less of an effect on virus entry. A PeV-A3 ELISA inhibition experiment, using an anti-PeV-A3 monoclonal antibody (mAb), suggested that POS binds directly to the PeV-A3 capsid. POS-resistant PeV-A3 strains developed by serial passage in the presence of POS, acquired substitutions in multiple regions of the genome, including the capsid. Reverse genetics confirmed substitutions in capsid proteins VP0, VP3, VP1 and nonstructural proteins 2A and 3A. Single mutants VP0_K66R, VP0_A124T, VP3_N88S, VP1_Y224C, 2A_S788L and 3A_T1I were respectively 4-, 9-, 12-, 34-, 51-, and 119-fold more resistant to POS than its susceptible prototype strain. Our studies demonstrate that POS may be a valuable tool in developing an antiviral therapy for PeV-A3.
Aseptic meningitis epidemics may pose various health care challenges.
We describe the German enterovirus meningitis epidemics in the university hospital centers of Düsseldorf, Cologne and Berlin between January 1st and December 31st, 2013 in order to scrutinize clinical differences from other aseptic meningitis cases.
A total of 72 enterovirus (EV-positive) meningitis cases were detected in our multicenter cohort, corresponding to 5.8% of all EV-positive cases which were voluntarily reported within the National Enterovirus surveillance (EVSurv, based on investigation of patients with suspected aseptic meningitis/encephalitis and/or acute flaccid paralysis) by physicians within this period of time. Among these 72 patients, 38 (52.8%) were enterovirus positive and typed as echovirus (18 pediatric and 20 adult cases, median age 18.5 years; echovirus 18 (1), echovirus 2 (1), echovirus 30 (31), echovirus 33 (1), echovirus 9 (4)). At the same time, 45 aseptic meningitis cases in our cohort were excluded to be due to enteroviral infection (EV-negative). Three EV-negative patients were tested positive for varicella zoster virus (VZV) and 1 EV-negative patient for herpes simplex virus 2. Hospitalization was significantly longer in EV-negative cases. Cerebrospinal fluid analysis did not reveal significant differences between the two groups. After discharge, EV-meningitis resulted in significant burden of sick leave in our pediatric cohort as parents had to care for the children at home.
Voluntary syndromic surveillance, such as provided by the EVSurv in our study may be a valuable tool for epidemiological research. Our analyses suggest that EV-positive meningitis predominantly affects younger patients and may be associated with a rather benign clinical course, compared to EV-negative cases.
Although Streptococcus agalactiae is the leading causative agent of neonatal sepsis and meningitis, recently it is increasingly isolated from non-pregnant adults. The relation between its presence in the genitourinary tract and manifested clinical symptoms of STD patients remains an open question. In this study, a complex epidemiological investigation of GBS isolates from a venerology clinic was performed.
Ninety-six GBS isolates were serotyped and their genetic relatedness determined by PFGE. MLST was also performed for a subset of 20 isolates. The antibiotic susceptibility was tested with agar dilution. Surface proteins and the ST-17 hypervirulent clone was detected by PCR.
The serotype prevalence was the following: V (29.2%), III (27.1%), Ia (22.9%), IV (10.4%), II (5.2%) and Ib (4.2%). A strong association was demonstrated between surface protein genes and serotypes. All isolates were fully susceptible to penicillin, but erythromycin and clindamycin resistance was high (41.7 and 35.4%, respectively), and 8 phenotypically macrolide sensitive isolates carried the ermB gene.
21.9% of all strains belonged to the hypervirulent ST17 clone, most being of serotype III and all were rib +. We found a few serotype IV isolates belonging to several STs and one serotype V/ST110 strain, containing a 44-bp deletion in the atr allele.
The presence of silent ermB genes is of worry, as their expression upon macrolide exposure could lead to unforeseen therapeutic failure, while clindamycin is used for intrapartum antibiotic prophylaxis, in case of penicillin allergy. The other alarming result is the high prevalence of ST17 among these strains from STD patients, who could be sources of further infections.
This is the first report from Hungary providing both serotyping and genotyping data of GBS isolates. These results could be helpful for vaccine production as the major vaccine candidates are capsular antigens or surface proteins.
Although antiretroviral therapy (ART) has greatly improved the prognosis of acquired immunodeficiency syndrome (AIDS) patients globally, opportunistic infections (OIs) are still common in Chinese AIDS patients, especially cryptococcosis.
We described here two Chinese AIDS patients with cryptococcal infections. Case one was a fifty-year-old male. At admission, he was conscious and oriented, with papulonodular and umbilicated skin lesions, some with ulceration and central necrosis resembling molluscum contagiosum. The overall impression reminded us of talaromycosis: we therefore initiated empirical treatment with amphotericin B, even though the case history of this patient did not support such a diagnosis. On the second day of infusion, the patient complained of intermittent headache, but the brain CT revealed no abnormalities. On the third day, a lumbar puncture was performed. The cerebral spinal fluid (CSF) was turbid, with slightly increased pressure. India ink staining was positive, but the cryptococcus antigen latex agglutination test (CrAgLAT: IMMY, USA) was negative. Two days later, the blood culture showed a growth of Cryptococcus neoformans, and the same result came from the skin culture. We added fluconazole to the patient’s treatment, but unfortunately, he died three days later.
Case two was a sixty-four-year-old female patient with mild fever, productive cough, dyspnea upon movement, and swelling in both lower limbs. The patient was empirically put on cotrimoxazole per os and moxifloxacin by infusion. A bronchofibroscopy was conducted with a fungal culture, showing growth of Cryptococcus laurentii colonies. Amphotericin B was started thereafter but discontinued three days later in favor of fluconazole 400 mg/d due to worsening renal function. The patient became afebrile after 72 h of treatment with considerable improvement of other comorbidities and was finally discharged with continuing oral antifungal therapy.
Our cases illustrate that cryptococcal disease is an important consideration when treating immunocompromised individuals such as AIDS patients. Life threatening meningitis or meningoencephalitis caused by C. neoformansmay still common in these populations and can vary greatly in clinical presentations, especially with regard to skin lesions. Pulmonary cryptococcosis caused by C. laurentii is rare, but should also be considered in certain contexts. Guidelines for its earlier diagnosis, treatment and prophylaxis are needed.
Giannoula S. Tansarli, Kimberle C. Chapin
The FilmArray® Meningitis/Encephalitis (ME) panel is a multiplex PCR assay which can detect the most commonly identified pathogens in central nervous system infections. It significantly decreases the time to diagnosis of ME and data has yielded several positive outcomes. However, in part, reports of both false positive and false negative detections have resulted in concerns about adoption.
A. Brik, A. Terrade, E. Hong, A. Deghmane, M.K. Taha, A. Bouafsoun, M. Khmiri, K. Boussetta, S. Boukhir, N. Ben Jaballah, A. Kechrid, H. Smaoui
Neisseria meningitidis (The meningococcus, Men) is a Gram-negative bacterium that cause meningitis and/or septicaemia. The virulence of Men is linked to many bacterial factors but the major one is the capsule. Based on the structure and the expression of the capsule, meningococcal strains are classified into 12 serogroups but Invasive Meningococcal Disease (IMD) is linked almost only to six of them: A, B, C, W, Y or X causing sporadic cases, small clusters or epidemics all over the world. However, the distribution of meningococcal serogroups varies in time and from country to another (Acevedo et al., 2019).
Saila, S., Gyanwali, G. C., Hussain, M., Gianfelice, A., Ireton, K.
Listeria monocytogenes is a food-borne bacterium that causes gastroenteritis, meningitis, or abortion. Listeria induces its internalization (entry) into some human cells through interaction of the bacterial surface protein InlB with its host receptor, the Met tyrosine kinase. InlB and Met promote entry through stimulation of localized actin polymerization and exocytosis. How actin cytoskeletal changes and exocytosis are controlled during entry is not well understood. Here we demonstrate important roles for the host GTPase Arf1 and its effectors AP1 and PICK1 in actin polymerization and exocytosis during InlB-dependent uptake. Depletion of Arf1 by RNAi or inhibition of Arf1 activity using a dominant negative allele impaired InlB-dependent internalization, indicating an important role for Arf1 in this process. InlB stimulated an increase in the GTP-bound form of Arf1, demonstrating that this bacterial protein activates Arf1. RNAi and immunolocalization studies indicated that Arf1 controls exocytosis and actin polymerization during entry by recruiting the effectors AP1 and PICK1 to the plasma membrane. In turn, AP1 and PICK1 promoted plasma membrane translocation of both Filamin A (FlnA) and Exo70, two host proteins previously found to mediate exocytosis during InlB-dependent internalization (M. Bhalla, H. Van Ngo, G.C. Gyanwali, and K. Ireton, Infect. Immun. 87: e00689-18. doi: 10.1128/IAI.00689-18). PICK1 mediated recruitment of Exo70, but not FlnA. Collectively these results indicate that Arf1, AP1, and PICK1 stimulate exocytosis by redistributing FlnA and Exo70 to the plasma membrane. We propose that Arf1, AP1, and PICK1 are key coordinators of actin polymerization and exocytosis during infection of host cells by Listeria.
N. Susilawathi et al.
Mizrahi, A., Marvaud, J. C., Pilmis, B., Nguyen Van, J. C., Couzigou, C., Bruel, C., Engrand, N., Le Monnier, A., Lambert, T.
We report a case of a 62-year old man treated for a Streptococcus pneumoniae meningitis by ceftriaxone and dexamethasone. After a neurological improvement, neurological degradation by vasculitis occurred, despite effective concentrations of ceftriaxone in serum and CSF. S. pneumoniae with increased MICs to third-generation-cephalosporins (3GC) was isolated from the ventricular fluid ten days after the isolation of the first strain. Isolates analysis showed that a mutation of penicillin-binding proteins in PBP2x has occurred under treatment.
Streptococcus oralis belongs to the Streptococcus mitis group and is part of the normal flora of the nasal and oropharynx (Koneman et al., The Gram-positive cocci part II: streptococci, enterococci and the ‘Streptococcus-like’ bacteria. Color atlas and textbook of diagnostic microbiology, 1997). Streptococcus oralis is implicated in meningitis in patients with decreased immune function or from surgical manipulation of the central nervous system. We report a unique case of meningitis by Streptococcus oralis in a 58-year-old patient with cerebral spinal fluid leak due to right sphenoid meningoencephalocele.
A 58-year-old female presented in the emergency department due to altered mental status, fevers, and nuchal rigidity. Blood cultures were positive for Streptococcus oralis. Magnetic resonance stereotactic imaging of head with intravenous gadolinium showed debris in lateral ventricle occipital horn and dural thickening/enhancement consistent with meningitis. There was also a right sphenoidal roof defect, and meningoencephalocele with cerebrospinal fluid leak as a result. The patient was treated with ceftriaxone and had endoscopic endonasal repair of defect. She had complete neurologic recovery 3 months later.
Cerebrospinal fluid leak puts patients at increased risk for meningitis. Our case is unique in highlighting Streptococcus oralis as the organism implicated in meningitis due to cerebrospinal fluid leak.
Simon F, Boutin J-P, Milleliri J-M, Tournier J-N. Cerebrospinal meningitis: lessons learnt from Africa. Lancet Infect Dis 2019; 19: 1056—In this Correspondence, the email address of the corresponding author should be email@example.com. This correction has been made to the online version as of Oct 9, 2019.
Hui-Han Chen, Andrew Stringer, Tadesse Eguale, Gauri G. Rao and Sachiko Ozawa
Antimicrobial resistance (AMR) is a growing threat to global health. Although AMR endangers continued effectiveness of antibiotics, the impact of AMR has been poorly estimated in low-income countries. This study sought to quantify the effect of AMR on treatments for pediatric pneumococcal disease in Ethiopia. We developed the DREAMR (Dynamic Representation of the Economics of AMR) model that simulate children younger than 5 years who acquire pneumococcal disease (pneumonia, meningitis, and acute otitis media) and seek treatment from various health facilities in Ethiopia over a year. We examined the AMR levels of three antibiotics (penicillin, amoxicillin, and ceftriaxone), treatment failures, and attributable deaths. We used the cost-of-illness method to assess the resulting economic impact of AMR from a societal perspective by estimating the direct and indirect treatment costs and productivity losses. Findings showed that AMR against antibiotics that were used to treat pneumococcal disease led to 195,763 treatment failures per year, which contributed to 2,925 child deaths annually in Ethiopia. Antimicrobial resistance resulted in a first-line treatment failure rate of 29.4%. In 1 year, the proportion of nonsusceptible Streptococcus pneumoniae bacteria increased by 2.1% and 0.5% for amoxicillin and penicillin, and reduced by 0.3% for less commonly used ceftriaxone. Annual costs of AMR to treat pneumococcal disease were around US$15.8 million, including US$3.3 million for ineffective first-line treatments, US$3.7 million for second-line treatments, and US$8.9 million for long-term productivity losses. Antibiotic stewardship to reduce misuse and overuse of antibiotics is essential to maintain the effectiveness of antibiotics, and lessen the health and economic burden of AMR.
Vimal Kumar Paliwal, Animesh Das, Sucharita Anand and Prabhakar Mishra
Intravenous (IV) dexamethasone is recommended for 14 days in stage 1 and 28 days in stage 2/3 tuberculous meningitis (TBM). We used a different steroid protocol. We shifted TBM patients to oral steroids after 48 hours of sustained improvement on IV steroids (oral group). Patients who worsened after shifting to oral steroids were reinitiated on IV steroids. Once they showed a consistent improvement for 48 hours, the IV steroids were overlapped with oral steroids for 7–10 days to taper off IV steroids (overlap group). We compared total IV steroid days in our patients with the recommended treatment and identified predictors that favored the oral group. This was a retrospective study. We included 98 patients with TBM (66 in the overlap group and 32 in the oral group) from January 2013 to July 2018. The median IV steroid days were 9 days (interquartile range of 4–12; 2–3.5 days in the oral group and 10–11.5 days in the overlap group). The mortality rate was 6.1%. The logistic regression model showed that TBM patients with basal exudate, tuberculoma, and modified Rankin scale (mRS) < 3 had a higher probability for going to the oral group. We conclude that total IV steroid days can be reduced in TBM patients by our method of steroid use. Presence of basal exudates and tuberculoma may favor early shifting from IV to oral steroid, whereas higher mRS may require a relatively longer course of IV steroid.
Mpoza E, Rajasingham R, Tugume L, et al.
AbstractBackgroundDetectable serum or plasma cryptococcal antigen (CrAg) precedes symptomatic cryptococcal meningitis. The World Health Organization (WHO) recommends CrAg screening for HIV infected people with CD4
Svensson E, Dian S, te Brake L, et al.
AbstractBackgroundIntensified antimicrobial treatment with higher rifampicin doses may improve outcome of tuberculous meningitis, but the desirable exposure and necessary dose are unknown. Our objective was to characterize the relationship between rifampicin exposures and mortality in order to identify optimal dosing for tuberculous meningitis.MethodsAn individual patient meta-analysis was performed on data from three Indonesian randomized controlled phase II trials comparing oral rifampicin 450mg (~10mg/kg) to intensified regimens including 750-1350mg orally, or a 600mg intravenous infusion. Pharmacokinetic data from plasma and CSF was analyzed with nonlinear mixed-effects modeling. Six-month survival was described with parametric time-to-event models.ResultsPharmacokinetic analyses included 133 individuals (1150 concentration measurements, 170 from CSF). The final model featured two disposition-compartments, saturable clearance and autoinduction. Rifampicin CSF concentrations were described by a partition coefficient (5.5% [95%CI 4.4-6.4]) and half-life for distribution plasma to CSF (2.1 h [1.3-2.9]). Higher CSF protein concentration increased the partition coefficient. Survival of 148 individuals (58 died, 15 drop-outs) was well described by an exponentially declining hazard, with lower age, higher baseline Glasgow Coma Scale score and higher individual rifampicin plasma exposure reducing the hazard. Simulations predicted an increase in 6-month survival from ~50% to ~70% upon increasing the oral rifampicin dose from 10 to 30mg/kg, and that higher doses would further increase survival.ConclusionsHigher rifampicin exposure substantially decreased the risk of death, and the maximal effect was not reached within the studied range. We suggest a rifampicin dose of at least 30mg/kg to be investigated in phase III clinical trials.
Invasive meningococcal disease (IMD) presenting with meningitis causes significant mortality and morbidity. Suppurative complications of serogroup B meningococcal sepsis are rare and necessitate urgent multidisciplinary management to mitigate long-term morbidity or mortality.
We present a rare case of invasive meningococcal disease in a 28-month old boy complicated by multiple abscess formation within a pre-existing antenatal left middle cerebral artery territory infarct. Past history was also notable for cerebral palsy with right hemiplegia, global developmental delay and West syndrome (infantile spasms). Two craniotomies were performed to achieve source control and prolonged antimicrobial therapy was necessary. The patient was successfully discharged following extensive multidisciplinary rehabilitation.
Longstanding areas of encephalomalacia in the left MCA distribution may have facilitated the development of multiple meningococcal serogroup B abscess cavities in the posterior left frontal, left parietal and left temporal lobes following an initial period of cerebritis and meningitis. A combination of chronic cerebral hypoperfusion and some degree of pre-existing necrosis in these areas, may also have facilitated growth of Neisseria meningitidis, leading ultimately to extensive cerebral abscess formation following haematogenous seeding during meningococcemia. In this case report we review similar cases of cerebral abscess or subdural empyema complicating serogroup B meningococcal meningitis.
Fiona Cresswell, Christoph Lange, Reinout van Crevel
Tuberculosis (TB) is the leading infectious cause of death globally. Meningitis accounts for 1-2% of TB cases (more in HIV-endemic settings), but kills or disables up to 50% or more of those affected . Tuberculous meningitis (TBM) is notoriously difficult to diagnose with conventional microbiological techniques due to the scarcity of bacilli and Mycobacterium tuberculosis DNA.
Cryptococcal meningitis is most commonly found in HIV-infected patients. In HIV-negative patients, its low incidence can lead to prolonged time to diagnosis. Detailed case reports of chronic cryptococcal meningitis are scarce, but could provide clues for earlier diagnosis in this patient category.
A 60-year old man presented June 2015 with intermittent headaches for several months without any fever. Initial work-up showed a leukocytosis, raised CSF opening pressure and raised leukocytes and protein in the CSF. An MRI revealed leptomeningeal contrast enhancement and cerebellar oedema. While malignancy and various infectious causes were excluded, the patient had a spontaneous clinical and radiological recovery. One year later, the patient returned with complaints of headaches. Also, cerebellar oedema and leptomeningeal contrast enhancement had recurred. Eventually in March 2017, the novel cryptococcal antigen lateral flow assay (CrAg LFA) was positive on CSF, and one colony of Cryptococcus neoformans was cultured from CSF. The patient was treated with the standard antifungal regimen which resulted in resolution of his headaches. In retrospect, the cryptococcal antigen test was already positive on a serum sample from June 2015. Interestingly, post-treatment immunological analysis revealed both a low mannose-binding lectin (MBL) concentration and low naïve CD4 counts.
We present a patient with cryptococcal meningitis in an HIV-negative patient with low MBL and low naïve CD4 count suffering a chronic relapsing meningo-encephalitis with relatively mild symptoms for around 2 years. In patients with an unexplained meningo-encephalitis such as this case, early performance of CrAg LFA on serum and/or CSF is an inexpensive and rapid method to reduce time-to diagnosis.
Chalermchai Somboonpatarakun, Pewpan M. Intapan, Oranuch Sanpool, Chaisiri Wongkham and Wanchai Maleewong
Angiostrongyliasis is a foodborne disease caused by a zoonotic nematode, Angiostrongylus cantonensis, which produces eosinophilic meningitis or meningoencephalitis (EOM) in humans. Definitive diagnosis is rarely possible because worms are almost never recovered from patients. Human disease can be diagnosed by clinical symptoms and serological tests. Presently, diagnosis is performed by serological detection of antibodies against specific somatic antigens (molecular mass 29–31 kDa) extracted from female worms. The life cycle of A. cantonensis must be maintained in the laboratory to provide a source of this diagnostic antigen. Here, we cloned and expressed recombinant A. cantonensis galectin-2 (rAcGal2) corresponding to a 31-kDa antigenic peptide. Recombinant protein was purified and used in immunoblot tests, which showed reactions with human serum panels consisting of six confirmed angiostrongyliasis and 24 clinically diagnosed cases of EOM-associated with angiostrongyliasis, 160 samples from patients with other parasitic infections, and 30 samples from normal healthy subjects. Accuracy, sensitivity, specificity, and positive and negative predictive values were 95.0%, 93.3%, 95.3%, 75.7%, and 98.9%, respectively. The test was nonreactive with sera of human gnathostomiasis and cysticercosis, two diseases that could present similar neurological symptoms. Recombinant AcGal2 has potential as a diagnostic antigen and could replace native parasite antigens in further development of an angiostrongyliasis serodiagnostic test kit.
Ortiz, S. C., Huang, M., Hull, C. M.
Spores are required for long-term survival of many organisms, including most fungi. For the majority of fatal human fungal pathogens, spore germination is the key process required to initiate vegetative growth and ultimately cause disease. Because germination is required for pathogenesis, the process could hold fungal-specific targets for new antifungal drug development. Compounds that inhibit germination could be developed into high efficacy, low-toxicity drugs for use in the prevention and/or treatment of fungal spore-mediated diseases. To identify drugs with the ability to inhibit pathogenic fungal spore germination, we developed a novel luciferase-based germination assay, using spores of the meningitis-causing yeast Cryptococcus. We screened the L1300 Selleck Library of FDA-approved drugs and identified 27 that inhibit germination. Of these, 22 inhibited both germination and yeast growth, and 21 have not been previously indicated for use in the treatment of fungal diseases. We quantitated the inhibition phenotypes of 10 specific germination/growth inhibitors in detail and tested one drug, the antiparasitic compound pentamidine, in our mouse intranasal model of cryptococcal infection. We discovered that pentamidine was effective at reducing lung fungal burdens when used in either prophylaxis (before infection) or treatment (after establishing an infection). Due to its efficacy in vivo and low intranasal toxicity, pentamidine is a lead candidate for repurposing for broader use as an antigerminant to prevent spore-mediated disease in immunocompromised patients. Not only does pentamidine provide an opportunity for prophylaxis against fungal spores, but it also provides proof of concept for targeting pathogenic spore germination for antifungal drug development.
Loenenbach A, van der Ende A, de Melker H, et al.
AbstractBackgroundAn increase in invasive meningococcal disease (IMD) serogroup W (IMD-W) cases caused by sequence type-11 clonal complex (cc11) was observed from October 2015 in the Netherlands. We compared the clinical picture and disease outcome of IMD-W cases with other serogroups, adjusting for host characteristics.MethodsWe included IMD cases reported from January 2015 to June 2018 in the Netherlands and assessed clinical manifestation and symptoms at disease onset and calculated case fatality rates (CFRs). We used logistic regression to compare clinical manifestations and mortality of IMD-W with IMD caused by meningococci serogroup B, Y, or C, adjusting for age, gender, and comorbidities.ResultsA total of 565 IMD cases were reported, of which 204 were IMD-W, 270 IMD-B, 63 IMD-Y, and 26 IMD-C. Most IMD-W isolates belonged to cc11 (93%; 175/188). Compared with other serogroups, IMD-W patients were diagnosed more often with septicemia (46%) or pneumonia (12%) and less often with meningitis (17%, P < .001). IMD-W cases presented more often with respiratory symptoms (45%, P < .001); 16% of IMD-W patients presented with diarrhea without IMD-specific symptoms (P = .061). The CFR for IMD-W was 16% (32/199, P < .001). The differences between IMD-W and other serogroups remained after adjusting for age, gender, and comorbidities.ConclusionsThe atypical presentation and severe outcome among IMD-W cases could not be explained by age, gender, and comorbidities. Almost all our IMD-W cases were caused by cc11. More research is needed to identify the bacterial factors involved in clinical presentation and severity of IMD-W cc11.
Invasive group B Streptococcus (GBS) disease in Chinese infants has gradually gained attention in recent years, but the molecular epidemiology of the pathogen is still not well known.
This multicenter study retrospectively investigated distribution of capsular serotypes, sequence types (STs), and hypervirulent GBS adhesin gene (hvgA) in clinical GBS isolates that caused invasive disease in infants aged
Ying Liu, Xiaohua Peng, Weizhen Weng, Jianyun Zhu, Hong Cao, Shibin Xie
A. J. Henningsson et al.
Non-typhoidal salmonellae (NTS) have been associated with invasive disease, notably meningitis, in immunocompromised individuals. Infections of this nature carry high rates of morbidity and mortality. Colistin resistance in salmonellae is a rare finding, more so in an invasive isolate such as cerebrospinal fluid (CSF). Colistin resistance has important infection control implications and failure to manage this phenomenon may lead to the loss of our last line of defence against multi-drug resistant Gram-negative organisms. To our knowledge, this is the first reported clinical case of colistin-resistant Salmonella Enteritidis meningitis in South Africa.
We report a case of a young male patient with advanced human immunodeficiency virus (HIV) infection who presented to hospital with symptoms of meningitis. Cerebrospinal fluid (CSF) cultured a Salmonella Enteritidis strain. Antimicrobial susceptibility testing (AST) of the isolate, revealed the strain to be colistin resistant. Despite early and aggressive antimicrobial therapy, the patient succumbed to the illness after a short stay in hospital. Subsequent genomic analysis of the isolate showed no presence of the mcr genes or resistance-conferring mutations in phoPQ, pmrAB, pmrHFIJKLME/arnBCADTEF, mgrB, and acrAB genes, suggesting the presence of a novel colistin resistance mechanism.
Invasive non-typhoidal salmonellae infection should be suspected in patients with advanced immunosuppression who present with clinical features of meningitis. Despite early and appropriate empiric therapy, these infections are commonly associated with adverse outcomes to the patient. Combination therapy with two active anti-Salmonella agents may be a consideration in the future to overcome the high mortality associated with NTS meningitis. Colistin resistance in clinical Salmonella isolates, although a rare finding at present, has significant public health and infection control implications. The causative mechanism of resistance should be sought in all cases.
Ana Helena A. Figueiredo, Matthijs C. Brouwer, Merijn W. Bijlsma, Arie van der Ende, Diederik van de Beek
Pneumonia is considered a focus of infection in patients presenting with community-acquired bacterial meningitis but the impact on disease course is unclear. The aim was to study presenting characteristics, clinical course and outcome of meningitis patients with co-existing pneumonia on admission.
Brink, M., Glimaker, M., Sjölin, J., Naucler, P.
Objectives Cefotaxime, alone or with ampicillin, is frequently used as empirical treatment of acute bacterial meningitis (ABM). Meropenem is a less investigated alternative. The aim of the study was to investigate the effects of empirical treatment with meropenem compared to cefotaxime plus ampicillin on outcome in ABM.Methods The study was based on data from the Swedish quality register for ABM between January 2008 and December 2016. A propensity score matching was performed to adjust for baseline differences between the groups. Mortality within 30-days was the primary outcome.Results The treatment regimens of interest were administered to 623 patients; 328 were given cefotaxime plus ampicillin whereas 295 received meropenem. After propensity score matching the 30-day mortality was 3.2% in the cefotaxime plus ampicillin group and 3.6% in the meropenem group. For matched cases the OR for 30-day mortality for meropenem vs. cefotaxime plus ampicillin was 1.15 (CI: 0.41–3.22; p=0.79). The OR for 90-day mortality was 1.47 (CI: 0.62–3.52; p=0.38), and for unfavorable outcome 1.10 (CI: 0.75–1.63; p=0.62).Conclusions The findings of our study indicate that meropenem is an effective empirical treatment option for adults with community-acquired ABM. However, to spare carbapenems, guidelines should continue to recommend third-generation cephalosporins as empirical treatment for the majority of patients with ABM.
Skipper C, Schleiss M, Bangdiwala A, et al.
AbstractBackgroundCryptococcal meningitis and tuberculosis are both important causes of death in persons with advanced HIV/AIDS. Cytomegalovirus (CMV) viremia may be associated with increased mortality in HIV-infected persons with tuberculosis. It is unknown if concurrent CMV viremia is associated with mortality in other AIDS-related opportunistic infections.MethodsWe prospectively enrolled HIV-infected Ugandans with cryptococcal meningitis from 2010–2012. Subsequently, we analyzed stored baseline plasma samples from 111 subjects for CMV DNA. We compared 10-week survival among those with and without CMV viremia.ResultsOf 111 participants, 52% (58/111) had detectable CMV DNA (median plasma viral load 498 IU/mL; IQR, 259–2390). All samples tested were positive on IgG serology. The median CD4+ T cell count was 19 cells/µL (IQR, 9–70) and did not differ by the presence of CMV viremia (P=.47). The 10-week mortality was 40% (23/58) in those with CMV viremia and 21% (11/53) in those without CMV viremia (Hazard Ratio=2.19; 95%CI, 1.07–4.49; P=.03), which remained significant after multivariate adjustment for known risk factors of mortality (adjusted Hazard Ratio=3.25; 95%CI, 1.49–7.10; P=.003). Serum and CSF cytokine levels were generally similar, and cryptococcal antigen-specific immune stimulation responses did not differ.ConclusionHalf of persons with advanced AIDS and cryptococcal meningitis had detectable CMV viremia. CMV viremia was associated with over two-fold higher mortality. It remains unclear whether CMV viremia in severely immunocompromised persons with cryptococcal meningitis contributes directly to this mortality or may reflect underlying immune dysfunction (i.e. cause vs. effect).
Zhang Z, Zhao S, Lian D, et al.
AbstractBackgroundStreptococcus pneumonia meningitis (PM) is a major cause of childhood neurological deficits. Although the Notch1 signalling pathway regulates neurogenesis and neuroinflammation, we know little about its expression or influence on hippocampal neurogenesis and gliogenesis during PM.MethodsWe used immunofluorescence and western blots to detect Notch1 signalling expression during experimental PM. Through double-labelling immunofluorescence, we investigated proliferation and differentiation in the dentate gyrus (DG) in PM before and after treatment with exogenous Notch1 activator (Jagged1) and inhibitor (IMR-1).ResultsOur results showed that Notch1 was activated after 24 h in PM. Compared with the PBS control, Jagged1 increased the proliferation of neural stem cells and progenitor cells (NS/PCs) in DG. After 14 and 28 d of meningitis, astrocyte differentiation increased compared with control. Astrocyte differentiation was higher in the Jagged1 versus the PBS group. In contrast, IMR-1 increased neuronal differentiation but decreased astrocyte differentiation compared with DMSO treatment.ConclusionUnder PM, Notch1 signalling promotes NS/PC proliferation and astrocyte differentiation in DG, while decreasing neuronal differentiation. Transient activation of the Notch1 signalling pathway explains the reactive gliogenesis and limited neuronal differentiation observed in PM.
G. Oligbu et al.
Coccidioides spp. are dimorphic fungi endemic to Central America, regions of South America and southwestern USA. Two species cause most human disease: Coccidioides immitis (primarily California isolates) and Coccidioides posadasii. Coccidioidomycosis is typically acquired through inhalation of soil or dust containing spores. Coccidioidal meningitis (CM), most common in the immunocompromised host, can also affect immunocompetent hosts.
We report a case of C. posadasii meningoencephalitis in a previously healthy 42-year-old Caucasian male who returned to Canada after spending time working in New Mexico. He presented with a 3-week history of headache, malaise and low-grade fevers. He developed progressive confusion and decreasing level of consciousness following hospitalization. Evidence of hydrocephalus and leptomeningeal enhancement was demonstrated on magnetic resonance imaging (MRI) of his brain. Serologic and PCR testing of the patient's CSF confirmed Coccidioides posadasii. Despite appropriate antifungal therapy he continues to have significant short-term memory deficits and has not returned to his full baseline functional status.
Travel to endemic regions can result in disease secondary to Coccidioides spp. and requires physicians in non-endemic areas to have a high index of suspicion. Effective therapeutic options have reduced the mortality rate of CM, however, it is still associated with significant morbidity and requires life-long therapy.
Management of partially-treated, community-acquired bacterial meningitis (PCBM) is commonly compromised by lack of microbiological diagnosis. We aimed to analyze the impact of FilmArray Meningitis-Encephalitis (FA-ME) PCR on the management of PCBM.
Comparison of treatment variables of PCBM cases between two periods, before (6.5 years, control group) and after (2 years, study group) the application of FA-ME PCR assay.
The total duration of antimicrobial treatment in the study group (n = 8) was significantly shorter than the control group (n = 23) (9.5 ± 3.7 days vs. 15.2 ± 5 days, p = 0.007). The percentage of narrow-spectrum regimens was significantly higher in the study group (78 ± 11% vs. 40 ± 9%, p = 0.03). There was a significant difference in implementation of antimicrobial chemoprophylaxis for close contacts (4/8 (50%) vs. 1/23 (4%), p = 0.01).
The use of FA-ME PCR provides significant benefits in the management of PCBM by shortening duration of antibiotic treatment, increasing the use of narrow-spectrum regimens, and allowing proper administration of antimicrobial chemoprophylaxis.
The study was approved and retrospectively registered by the Tel-Aviv Sourasky Medical Center (0378–17-TLV, 10/17/2017) and Rabin Medical Center (0270–18-RMC, 11/11/2018) Ethics committees and conforms to recognized standards.
Ravi Shekhar Jaipuriar, Ravindra Kumar Garg, Imran Rizvi, Hardeep Singh Malhotra, Neeraj Kumar, Amita Jain, Rajesh Verma, Praveen Kumar Sharma, Shweta Pandey and Ravi Uniyal
Most deaths in tuberculous meningitis occur in the early part of the illness. We assessed the determinants of early deaths, occurring within 2 months of intensive therapy. We prospectively included consecutive newly diagnosed adults with HIV-negative tuberculous meningitis. Patients were given WHO-recommended antituberculosis treatment and were followed up for 9 months. We enrolled 152 patients. A total of 26 deaths were recorded during 2 months. The logistic regression analysis revealed that papilledema (P = 0.029, odds ratio (OR) = 4.8 [1.2–19.8]), increasing age (P = 0.001, OR = 1.07 [1.03–1.1]), stage-III disease (Glasgow coma scale score ≤ 10; P = 0.01, OR = 4.2 [1.4–12.3]), and hydrocephalus (P = 0.003, OR = 8.4 [2.1–33.6]) were independently associated with death. In addition, cerebral infarcts (P = 0.012, OR = 5.6 [1.5–21.3]), paraparesis (P = 0.004, OR = 8.8 [2.02–38.1]), and age (P = 0.005, OR = 1.05 [1.02–1.09]) were associated with poor functional outcome. In conclusion, disease severity predicts early deaths in tuberculous meningitis.
Ji-Soo Kwon, Joung Ha Park, Ji Yeun Kim, Hye Hee Cha, Min-Jae Kim, Yong Pil Chong, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Jun Hee Woo, Yong Seo Koo, Sang-Beom Jeon, Sang-Ahm Lee and Sung-Han Kim
In this study, we investigated the diagnostic utility of the cytokine profile of the cerebrospinal fluid (CSF) and enzyme-linked immunospot (ELISPOT) assays of patients with suspected tuberculous meningitis (TBM). We prospectively enrolled adult patients with suspected TBM, and CSF specimens were analyzed for 18 cytokines/chemokines and soluble programmed death protein 1 (PD-1) and programmed death ligand 1 (PD-L1). Enzyme-linked immunospot assays were performed on mononuclear cells from the CSF (CSF-MCs) and peripheral blood (PBMCs). A total of 87 patients with meningitis, including 42 TBM-suspected patients and 45 non-TBM patients, were enrolled. Excluding the 32 patients with possible TBM, 10 patients with TBM and 45 patients with non-TBM were finally analyzed. Levels of adenosine deaminase (ADA), interleukin 12 subunit β (IL-12p40), IL-13, macrophage inflammatory protein α (MIP-1α), and soluble PD-1 and PD-L1 in the CSF were significantly higher in the TBM group than in the non-TBM group (P < 0.05). The optimal cutoff values for the sensitivities and specificities of the test methods for diagnosing TBM with small samples of 10 cases of definite or probable TBM were as follows: ADA > 6.95 U/L, 70% and 81%; IL-12p40 > 52.04 pg/mL, 80% and 73%; IL-13 > 0.44 pg/mL, 90% and 47%; MIP-1α > 8.83 pg/mL, 80% and 62%; soluble PD-1 > 35.87 pg/mL, 80% and 63%; soluble PD-L1 > 24.19 pg/mL, 80% and 61%; CSF-MC ELISPOT > 13.5 spots/250,000 CSF-MC, 30% and 91%; and PBMC ELISPOT > 14 spots/250,000 PBMCs, 50% and 78%, respectively. Therefore, CSF IL-12p40, IL-13, MIP-1α, and soluble PD-1 and PD-L1 concentrations appear to be useful adjuncts for diagnosing TBM.
Specialespecifikt kursus om immundefekt og feber af ukendt årsag
28.01.2020 - 29.01.2020
International Congress on Infectious Diseases (ICID) 2020
Kuala Lumpur, Malaysia
20.02.2020 - 23.02.2020
Dansk Selskab for Intern Medicin (DSIM) årsmøde og overrækkelse af Hagedorn prisen 2020
Novo Nordisk Fonden, Tuborg Havnevej 19, 2900 Hellerup
Conference on Retroviruses and Opportunistic Infections (CROI) 2020
Boston, Massachusetts, USA
8.03.2020 - 11.03.2020
Når CROI går i fisk - med transmissioner fra CROI 2020
10.03.2020 - 11.03.2020
Retningslinjer til sundhedsprofessionelle vedr. håndtering af infektion med zikavirus (2019)
Antiviral behandling af hiv smittede personer (2019)
Lumbalpunktur af patienter i blodfortyndende behandling (2019)
Single dose of Doxycycline for the prevention of TBRF
19.01.2020Clinical Infectious Diseases Advance Access
Characteristics of invasive pneumococcal disease (IPD) caused by emerging serotypes after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in England; prospective observational cohort study, 2014-18
19.01.2020Clinical Infectious Diseases Advance Access
The effect of therapeutic drug monitoring of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients: the DOLPHIN trial protocol of a multi-centre randomised controlled trial
17.01.2020Latest Results for BMC Infectious Diseases
Fatal hemorrhagic varicella in a patient with abdominal pain: a case report
17.01.2020Latest Results for BMC Infectious Diseases
Antifungal resistance in patients with Candidaemia: a retrospective cohort study
17.01.2020Latest Results for BMC Infectious Diseases
Hvad tænker Professor Jens Lundgren om"Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV."?
Hvad synes Professor Troels Lillebæk om"The global prevalence of latent tuberculosis: a systematic review and meta-analysis."?
Hvad synes Professor Lars Østergaard om"Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial."?
Hvad synes Professor Thomas Benfield om"Oral versus Intravenous Antibiotics for Bone and Joint Infection."?
Hvad mener Professor Niels Obel om artiklen"Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis."?
Indtast din email for at tilmelde dig vores nyhedsbrev og hold dig opdateret om nyt på hjemmesiden.
© 2020 Dansk Selskab for Infektionsmedicin
version: 2.6.0 ● design: C P Fischer
Side indlæst på 0,251 s