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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
Stroke has relevant morbidity and mortality despite appropriate treatments and early diagnosis. Beside common risk factors such as diabetes and atrial fibrillation, infections can be involved in stroke pathogenesis, probably causing a systemic release of cytokines and other inflammatory mediators, triggering a latent pro-thrombotic state or damaging the vascular endothelium. In other cases, infections can occur as stroke-like syndromes, requiring a high grade of suspicion to avoid a delay in establishing a correct diagnosis.
Treatment of stroke or stroke-like syndromes of infectious origin can be difficult. When a previous infective event triggers stroke, Alteplase administration can be associated with a higher incidence of bleeding and the extension of the ischaemic area can be major than expected. On the other hand, when stroke is part of some infectious diseases’ presentation as in endocarditis, bacterial or tuberculous meningitis and meningo-vascular syphilis, a correct diagnosis can be difficult. The management of these stroke-like syndromes is not standardised because common treatments proven to be effective for patients with stroke of vascular origin can worsen the prognosis, as it can be demonstrated after to be incorrect Alteplase administration to patients with endocarditis with septic embolism to the brain is associated with an increase of the risk of haemorrhage.
Stroke or stroke-like syndrome of infectious origin can be observed in an important proportion of case presenting with sensory-motor deficit of unknown origin; their accurate diagnosis has a considerable impact in terms of treatment choices and outcome.
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.
Alexander Stebner, Armin Ensser, Walter Geißdörfer, Yavor Bozhkov, Roland Lang
Brain abscesses lead to high mortality despite antibiotic and surgical treatment. Identification of causative bacteria is important to guide antibiotic therapy, but culture-based methods and molecular diagnostics by Sanger sequencing of 16S PCR products are hampered by antibiotic treatment and the often polymicrobial nature of brain abscesses. We have applied 16S rRNA-based next generation sequencing (NGS) for metagenomic analysis of intracranial (brain and epidural) abscess and meningitis samples.
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.
A year spent working in a township hospital outside Cape Town, South Africa, was a defining career moment for Sean Wasserman, winner of the 2019 Stephen Lawn TB-HIV Research Leadership Prize, which is supported by The Union. “I remember seeing the devastation caused by untreated HIV and common opportunistic infections including TB and meningitis, and was inspired by the high quality of medicine practised by my consultants in this challenging environment. I knew from that point on that I wanted to make a contribution in the emerging field of infectious diseases medicine in South Africa”, he says.
Streptococcus suis is a zoonotic pathogen that causes serious systemic infections in pigs and occupation-related infections in humans who contact with pigs or pork products. In China, it has caused two outbreaks of human infection and surveillance for S.suis has been ongoing since last time.
Two cases of meningitis and sepsis caused by S. suis were reported in this study. Both patients work in relation to the pork trade, a risk factor for S. suis infection. The outcome was favorable after a prolonged ceftriaxone therapy but one patient was left with mild hearing loss. Two isolates were identified as sequencing type (ST) 7, S. suis serotype 2 (SS2), which is one the most prevalent and cause two outbreaks in China. Whole-genome sequencing (WGS) revealed that a high degree identity was noted in the genome organizations and sequences between two sporadic ST7 SS2 isolates in this study and representative epidemic virulent isolates. Major differences among them are two sporadic ST7 SS2 isolates lacked a virulence factor called agglutinin receptor and an 89 K pathogenicity island (PAI), which plays important role in the pathogenesis of streptococcal toxic shock syndrome (STSS). A summary about STs of human infection with S. suis in China was completed. The result showed ST1 and ST7 were still the major STs and several novel STs were successfully discovered in different provinces.
Our results enhanced the understanding of the ability to cause life-threatening infections in humans and the distribution and evolution of the S. suis in China.
The Choosing Wisely® initiative is an international campaign addressing over- and underuse of diagnostic and therapeutic measures in infectious diseases among others. Since 2016, the German Society for Infectious Diseases (DGI) has constantly designed new items in this regard. Here we report the most recent recommendations.
The recommendations of the DGI are part of the “Klug entscheiden” initiative of the German Society of Internal Medicine (DGIM). Topics for the new items were suggested by members of the DGI, checked for scientific evidence and consented within the DGI and the DGIM before publication.
The new recommendations are: (1) individuals with immune-suppression, advanced liver cirrhosis or renal insufficiency should receive a dual pneumococcal vaccination. (2) In case of positive blood cultures with Candida spp. thorough diagnostics and treatment should be initiated. (3) In case of suspected meningitis, adult patients should receive dexamethasone and antibiotics immediately after venipuncture for blood cultures and before potential imaging. (4) In case of suspected meningitis a CT scan before lumbar puncture should not be ordered—except for symptoms indicating high CSF pressure or focal brain pathology or in cases of severe immune-suppression. (5) In patients with suspected severe infections, a minimum of two pairs of blood cultures should be drawn using separate venipunctures prior to antibiotic therapy—regardless of body temperature. There is no need of a minimum time interval in between the blood draws.
Applying these new Choosing Wisely® recommendations will increase patient safety and the value of health care.
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.
Waking shivering in the night, Michelle Bryden assumed she had flu, and took the following day off work. But then her feet and hands started to turn purple. In fact, she had contracted bacterial meningitis caused by Streptococcus pneumoniae and was admitted to Howard County General (Columbia, MD), where she was eventually diagnosed with sepsis. At the time, in April 2019, Michelle was a healthy, active 48-year-old, with a passion for gardening, who worked at Johns Hopkins Applied Physics Laboratory (Laurel, MD, US) as an engineer.
Pontus Nauclér, Angela Huttner, Cornelis H. van Werkhoven, Mervyn Singer, Pierre Tattevin, Sharon Einav, Thomas Tängdén
Rapid initiation of antibiotic treatment is considered crucial in patients with severe infections such as septic shock and meningitis but may not be as important for other infectious syndromes. A better understanding of which patients can tolerate a delay in start of therapy is important for antibiotic stewardship purposes.
Kassis C, Durkin M, Holbrook E, et al.
AbstractBackgroundAntibody detection is the main method for diagnosis of coccidioidomycosis but has limitations. The Coccidioides antigen enzyme immunoassay is recommended for testing cerebrospinal fluid in suspected meningitis. Reports on urine and serum antigen detection evaluated small numbers of patients who were mostly immunocompromised. The purpose of this study was to assess the accuracy of combined antibody and antigen detection for diagnosis.MethodsA retrospective study, including all patients in whom Coccidioides antigen detection in serum was performed between January 2013 and May 2017 was conducted at Valleywise Health Medical Center (formerly Maricopa Integrated Health System). Sensitivity and specificity of antigen and antibody were evaluated in 158 cases and 487 controls.ResultsThe sensitivity of antibody detection by ID was 84.2%. The sensitivity of antigen detection was 57.0% if both urine and serum were tested and 36.7% if urine alone was tested. The sensitivity of combining antigen and ID antibody detection was 93.0%. The sensitivity of urine and serum antigen detection was 55.4% in proven and 58.7% in probable cases, 79.1% in disseminated and 41.6% in pulmonary cases, 74.7% in immunocompromised and 40.0% in immunocompetent patients. Specificity was 99.4% for antigen detection and 96.5% for ID antibody detection. Diagnostic accuracy was 95.4% for ID antibody and antigen detection, 93.6% for ID antibody alone and 89.1% for pathology or culture.ConclusionsThese findings support combined antibody and antigen detection for diagnosis of progressive coccidioidomycosis. The diagnosis may have been missed if antigen detection was not performed.
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.
Fever is a cause for concern for both parents and the treating pediatrician and a common reason for antibiotic overuse. However, the proportion of children hospitalized for fever with serious bacterial infection (SBI) is uncertain. We aimed to evaluate the epidemiological, clinical, hematological, and biochemical risks for SBI among the children admitted with fever.
This prospective study was conducted in a rural teaching hospital in India on consecutive children, aged 3 months–12 years, presenting with fever 100 °F (37.7 °C) or higher. The presence of SBI was confirmed with one of the following criteria: (a) a positive blood culture; (b) roentgenographically confirmed pneumonia with high titres of C-reactive protein; (c) a culture-confirmed urinary tract infection; (d) enteric fever diagnosed clinically in addition to either a positive blood culture or high Widal titers; and (e) meningitis diagnosed clinically in addition to either a positive blood culture or cerebrospinal fluid culture. A predefined questionnaire was filled.
A total of 302 children were included in the study, out of which 47% (95% CI 41.4–52.7%) presented with SBI. The factors associated with confirmed SBI in bivariate analysis were history of previous hospitalization, history of chronic illness, history of medication in the previous 1 week, a partially immunized child, history of common cold, moderate-grade fever, toxic look, significant lymphadenopathy, absence of BCG scar, delayed development, irritability, breathlessness, respiratory distress, poor feeding, significant weight loss, suspected urinary tract infection, hyponatremia, hypokalemia, and abnormal leucocyte count. The final generalized logistic regression model revealed partially immunized child (RR 4.26), breathlessness (RR 1.80), weight loss (RR 2.28), and suspected urinary tract infection (RR 1.95) as risk factors for the increased risk of SBI.
The study identified multiple risk factors for SBI. Pediatricians can be made aware of these risk factors. Further studies are warranted to identify age-specific risk factors for SBI because most clinicians depend on clinical signs and symptoms to identify SBI.
McGee L, Chochua S, Li Z, et al.
AbstractBackgroundGroup B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis and an important cause of invasive infections in pregnant and nonpregnant adults. Vaccines targeting capsule polysaccharides and common proteins are under development.MethodsUsing whole genome sequencing (WGS), a validated bioinformatics pipeline, and targeted antimicrobial susceptibility testing, we characterized 6,340 invasive GBS recovered during 2015-2017 through population-based Active Bacterial Core surveillance (ABCs) in eight states.ResultsSix serotypes accounted for 98.4% of isolates (21.8% Ia, 17.6% V, 17.1% II, 15.6% III, 14.5% Ib, 11.8% IV). Most (94.2%) isolates were in eleven clonal complexes (CCs) comprised of multilocus sequence types (MLSTs) identical or closely related to STs 1, 8, 12, 17, 19, 22, 23, 28, 88, 452 and 459. Fifty-four isolates (0.87%) had point mutations within pbp2x associated with non-susceptibility to one or more β-lactam antibiotics. Genes conferring resistance to macrolides and/or lincosamides were found in 56% of isolates; 85.2% of isolates had tetracycline resistance genes. Two isolates carrying vanG were vancomycin-nonsusceptible (MIC 2µg/ml). Nearly all isolates possessed capsule genes, 1-2 of the three main pilus gene clusters, and one of four homologous Alpha/Rib family determinants. Presence of hvgA virulence gene was primarily restricted to serotype III/CC17 isolates (465 isolates), but 8 exceptions (7 IV/CC452 and 1 IV/CC17) were observed.ConclusionsThis first comprehensive, population-based quantitation of strain features in the United States suggests current vaccine candidates should have good coverage. Beta-lactams remain appropriate for first line treatment and prophylaxis, but emergence of nonsusceptibility warrants ongoing monitoring.
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.
Anne T. Kloek, Matthijs C. Brouwer, Ben Schmand, Michael W.T. Tanck, Diederik van de Beek
We performed a cross sectional cohort study on long-term neurologic, cognitive, and quality of life outcome in adults surviving pneumococcal meningitis.
OuYang, X., Guo, J., Lv, Q., Jiang, H., Zheng, Y., Liu, P., Zhao, T., Kong, D., Hao, H., Jiang, Y.
Streptococcus suis (S. suis) is an emerging zoonotic agent that causes streptococcal toxic shock-like syndrome (STSLS) and meningitis in humans, with high mortality and morbidity. The pathogenesis of both STSLS and CNS infections caused by S. suis is not well understood. TRIM32, a member of the tripartite motif (TRIM) protein family, has been reported to regulate host inflammatory responses. In this study, we show that TRIM32 deficiency significantly reduced the level of bacteremia and the production of proinflammatory cytokines following severe S. suis infection, protecting infected mice from STSLS. The influence of TRIM32 gene deletion on a range of processes known to be involved in S. suis meningitis was also examined. Both bacterial loads and indications of brain hemorrhage were reduced in infected Trim32-/- mice compared with infected wild-type (WT) controls. We also found that TRIM32 deficiency increased the permeability of the blood-brain barrier (BBB) and the recruitment of inflammatory monocytes during the early course of S. suis infection, potentially limiting the development of S. suis meningitis. Our results suggest that TRIM32 sensitizes S. suis-induced infection via innate immune response regulation.
Trevijano-Contador, N., Pianalto, K. M., Nichols, C. B., Zaragoza, O., Alspaugh, J. A., Pirofski, L.-a.
Human studies have shown associations between cryptococcal meningitis and reduced IgM memory B cell levels and studies in IgM and/or B cell deficient mice have demonstrated increased Cryptococcus neoformans (C. neoformans) dissemination from lungs to brain. Since immunoglobulins are part of the immune milieu that C. neoformans confronts in a human host, and its ability to form Titan cells is an important virulence mechanism, we determined the effect of human immunoglobulins on C. neoformans Titan cell formation in vitro. 1) Fluorescence microscopy showed normal human IgG and IgM bind C. neoformans. 2) C. neoformans grown in Titan cell-inducing medium with IgM, not IgG, inhibited Titan-like cell formation. 3) Absorption of IgM with laminarin or curdlan (branched and linear 1-3-beta D glucans, respectively) decreased this effect. 4) Transmission electron microscopy revealed that cells grown with IgM had small capsules and unique features not seen with cells grown with IgG. 5) Comparative transcriptional analysis of cell wall, capsule, and stress response genes showed that C. neoformans grown with IgM, not IgG or PBS, had decreased expression of chitin synthetase, CHS1, CHS2, and CHS8, and genes encoding cell wall carbohydrate synthetases α-1-3-glucan (AGS1) and β-1,3-glucan (FKS1). IgM also decreased expression of RIM101 and HOG1, genes encoding central regulators of C. neoformans stress response pathways and cell morphogenesis. Our data show human IgM affects C. neoformans morphology in vitro and suggest that the hypothesis that human immunoglobulins may affect C. neoformans virulence in vivo warrants further investigation.
Cryptococcal meningitis (CM) is the most common fungal infection of the central nervous system and has high morbidity and mortality. Almost studies about prognostic factors have largely focused on the immunocompromised population rather than immunocompetent patients. So that we sought to conduct a retrospective study to determine prognostic factors which predict the outcomes in immunocompetent patients with CM.
We retrospectively collected and analyzed the demographic and clinical data of 76 apparently immunocompetent patients with cryptococcal meningitis from January 2003 to June 2019 in China. The clinical outcome was graded by the Glasgow outcome scale (GOS) at discharge, and patients were divided into good (score of 5) and unfavorable (score of 1–4) outcome groups, potential prognostic factors were analyzed.
Non-parametric test confirmed that unfavorable outcome was associated with lower glucose level of CSF(P = 0.001), and Pearson’s χ2 analysis confirmed that unfavorable outcome was associated with opening pressure of CSF(>300mmH20, P = 0.038), impaired consciousness (P = 0.001), hydrocephalus(P = 0.045), and Shunt surgery (P = 0.045), and then multiple logistic regression analysis confirmed that impaired consciousness(P = 0.015) and lower glucose concentration of CSF(P = 0.012) increased the likelihood of unfavorable outcome in CM patients.
Impaired consciousness and decreased glucose concentration of CSF were independently prognostic factors which predict the unsatisfactory outcome in immunocompetent patients with CM.
Delbaz, A., Chen, M., Jen, F. E.- C., Schulz, B. L., Gorse, A.-D., Jennings, M. P., St John, J. A., Ekberg, J. A. K.
Neisseria meningitidis, a common cause of sepsis and bacterial meningitis, infects the meninges and central nervous system (CNS) primarily via paracellular traversal across the blood-brain or blood-cerebrospinal fluid barrier. N. meningitidis is often present asymptomatically in the nasopharynx, and the nerves extending between the nasal cavity and the brain constitute an alternative route by which the meningococci may reach the CNS. To date, the cellular mechanisms involved in nerve infection are not fully understood. Peripheral nerve glial cells are phagocytic and capable of eliminating microorganisms, but some pathogens may be able to overcome this protection mechanism and instead infect the glia, causing cell death or pathology. Here, we show that N. meningitidis readily infects trigeminal Schwann cells (the glial cells of the trigeminal nerve) in vitro in both two-dimensional and three-dimensional cell cultures. Infection of trigeminal Schwann cells may be one mechanism by which N. meningitidis is able to invade the CNS. Infection of the cells led to multinucleation and the appearance of atypical nuclei, with the presence of horseshoe nuclei and budding of nuclei increasing over time. Using SWATH-MS proteomics followed by bioinformatics pathway analysis, we showed that N. meningitidis induced protein alterations in the glia associated with altered intercellular signalling, cell-cell interactions and cellular movement. The analysis also suggested that the alterations in protein levels were consistent with changes occurring in cancer. Thus, infection of the trigeminal nerve by N. meningitidis may have ongoing adverse effects on the biology of Schwann cells, which may lead to pathology.
Cryptococcal meningitis (CCM) is a common and deadly disease among HIV-infected patients. Notable about CCM is its association with the immune reconstitution inflammatory syndrome (IRIS). Though it has been posited a switch from first to second-line antiretroviral therapy (ART) can induce CCM IRIS, a case presentation of CCM IRIS has not been published.
A 10-year-old, HIV-infected girl who initially presented with severe headache and new-onset seizures, with cerebrospinal fluid that returned antigen, India Ink, and culture positive for Cryptococcus neoformans. Notably, 8 weeks prior to seizures, she had switched from first line to second-line ART (abacavir-lamivudine-efavirenz to zidovudine-lamivudine-lopinavir/ritonavir) due to virologic failure, with a viral load of 224,000 copies/milliliter. At time of seizures and 8 weeks on second-line ART, her viral load had reduced to 262 copies/milliliter.
Her hospital course was prolonged, as she had ongoing headaches and developed bilateral cranial nerve VI palsies despite clearance of Cryptococcus from cerebrospinal fluid on antifungal therapy and therapeutic lumbar punctures. However, symptoms stabilized, and she was discharged with oral fluconazole. Cranial nerve palsies resolved 10 weeks post discharge and she has remained disease free.
We describe a case of CCM IRIS in a 10-year-old HIV infected child after changing to second-line ART. This case provides evidence that screening for cryptococcal antigenaemia prior to switch from first-line to second-line ART could be an important measure to prevent cryptococcal disease.
Frederik Federspiel, Sofie Skovmand, Sigurdur Skarphedinsson
Tam T. Van, Tae Hun Kim, Susan M. Butler-Wu
Cryptococcal meningitis (CM) remains an important cause of morbidity and mortality among immunocompromised patients. Laboratory diagnostics for CM includes antigen detection, staining, and culture. Data on the performance of the Biofire® FilmArray® Meningitis/Encephalitis (ME) Panel for detecting Cryptococcus neoformans/gattii is limited, with several reports describing false negativity for this target.
Cryptococcal antigen (CrAg) screening with fluconazole prophylaxis has been shown to prevent cryptococcal meningitis and mortality for people living with HIV (PLWH) with CD4
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.
International Liver Congress (ILC) 2020
15.04.2020 - 19.04.2020
European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2020
18.04.2020 - 21.04.2020
DSI årsmøde 2020 (aflyst)
Hindsgavl Slot, Middelfart
1.05.2020 - 2.05.2020
Kursus i rejsemedicin 2020
Statens Serum Institut
4.05.2020 - 6.05.2020
5.05.2020 - 7.05.2020
COVID-19 retningslinje (2020)
National handlingsplan for antibiotika til mennesker (2017)
Retningslinjer til sundhedsprofessionelle vedr. håndtering af infektion med zikavirus (2019)
Antiviral behandling af hiv smittede personer (2019)
Genetic Characterization of Japanese Encephalitis Virus Genotype 5 Isolated from Patient, South Korea, 2015
6.04.2020Emerging Infectious Diseases Journal
Rhizopus microsporus Infections Associated with Surgical Procedures, Argentina, 2006–2014
6.04.2020Emerging Infectious Diseases Journal
6.04.2020Emerging Infectious Diseases Journal
Diplorickettsia Bacteria in an Ixodes scapularis Tick, Vermont, USA
6.04.2020Emerging Infectious Diseases Journal
Fatal Rodentborne Leptospirosis in Prison Inmates, South Africa, 2015
6.04.2020Emerging Infectious Diseases Journal
Hvorfor anbefaler Professor Jens Lundgren artiklen"Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV."?
Hvad tænker 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 tænker 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."?
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