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Clinical Microbiology and Infection :... Dec 2022Rapid and accurate diagnosis of herpes simplex virus (HSV)-1 and -2 (HSV1/2) in cerebrospinal fluid (CSF) is important for patient management. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Rapid and accurate diagnosis of herpes simplex virus (HSV)-1 and -2 (HSV1/2) in cerebrospinal fluid (CSF) is important for patient management.
OBJECTIVES
Summarize the diagnostic accuracy of commercial rapid sample-to-answer PCR assays (results in <90 minutes, without a separate nucleic acid extraction step) for HSV1/2 detection in CSF.
DATA SOURCES
Four databases (MEDLINE, EMBASE, Scopus, and CENTRAL) and five conference abstract datasets from January 2012 to March 2022.
STUDY ELIGIBILITY CRITERIA
Eligible diagnostic accuracy studies provided sufficient data for the construction of a standard diagnostic accuracy two-by-two table.
PARTICIPANTS
Patients with suspected meningitis and/or encephalitis.
TESTS
FilmArray Meningitis-Encephalitis Panel and Simplexa HSV 1&2 Direct Kit PCR.
REFERENCE STANDARD
Real-time PCR assay.
ASSESSMENT OF RISK OF BIAS
Two investigators independently extracted data, rated risk of bias, and assessed quality using QUADAS-2. METHODS OF DATA SYNTHESIS: Accuracy estimates were pooled using Bayesian random effects models.
RESULTS
Thirty-one studies were included (27 FilmArray; 4 Simplexa), comprising 9924 samples, with 95 HSV-1 and 247 HSV-2 infections. Pooled FilmArray sensitivities were 84.3% (95% credible interval, 72.3-93.0) and 92.9% (95% credible interval (CrI), 82.0-98.5) for HSV-1 and HSV-2, respectively; specificities were 99.8% (95% CrI, 99.6-99.9) and 99.9% (95% CrI, 99.9-100). Pooled Simplexa sensitivities were 97.1% (95% CrI, 88.1-99.6) and 97.9% (95% CrI, 89.6-99.9), respectively; specificities were 98.9% (95% CrI, 96.8-99.7) and 98.9% (95% CrI, 97.1-99.7). Pooled FilmArray sensitivities favoured industry-sponsored studies by 10.0 and 13.0 percentage points for HSV-1 and HSV-2, respectively. Incomplete reporting frequently led to unclear risk of bias. Several FilmArray studies did not fully report true negative data leading to their exclusion.
CONCLUSIONS
Our results suggest Simplexa is accurate for HSV1/2 detection in CSF. Moderate FilmArray sensitivity for HSV-1 suggests additional testing and/or repeat CSF sampling is required for suspected HSV encephalitis when the HSV-1 result is negative. Low prevalence of HSV-1 infections limited summary estimates' precision. Underreporting of covariates limited exploration of heterogeneity.
Topics: Humans; Herpesvirus 1, Human; Bayes Theorem; Sensitivity and Specificity; Encephalitis, Herpes Simplex; Real-Time Polymerase Chain Reaction; Meningitis; Cerebrospinal Fluid
PubMed: 35718347
DOI: 10.1016/j.cmi.2022.06.004 -
Therapeutic Advances in Infectious... 2021In India, owing to multiple factors, such as insufficient laboratory capacity, poor reporting systems due to limited access to healthcare facilities and limited disease... (Review)
Review
BACKGROUND
In India, owing to multiple factors, such as insufficient laboratory capacity, poor reporting systems due to limited access to healthcare facilities and limited disease surveillance programmes, the actual disease burden of meningitis is unknown and may be largely under-reported.
OBJECTIVE
A systematic literature review was performed to describe: (a) the prevalence of meningitis; and (b) its etiological pathogen across different regions, age groups and patients with comorbidities.
METHOD
A systematic literature search was conducted between 1990 and 2020 using PubMed and Google Scholar databases to identify Indian studies reporting the prevalence rates and etiology of meningitis. A total of 51 studies were included in the final analysis.
RESULTS
A total of 38 studies reported prevalence of meningitis and 21 studies reported data on the etiology of meningitis in India. These studies included mixed patient populations: (a) pyogenic meningitis; (b) meningitis in sick or hospitalized patients with tuberculosis, acute febrile encephalopathy syndrome, septicaemia, invasive pneumococcal disease or respiratory compromise; and (c) meningitis patients with comorbidities. The prevalence of confirmed bacterial meningitis in the pediatric population (0-14 years) ranged between 0.5% and 61.8%. A total of seven studies reported the prevalence of meningitis in patients of all age groups (0-75 years), with prevalence ranging between 8.68% and 78.85%. Cryptococcal meningitis was predominant in patients with positive HIV/AIDS, with a prevalence ranging between 2.09% and 53.1%. was found to be the predominant pathogen causing meningitis across different regions of India, with a frequency ranging from 4% to 61.8% in patients of all age groups.
CONCLUSION
This systematic literature review displayed the possible range of frequency of bacterial meningitis pathogens across a wide variety of age groups in different regions of India. Further studies are warranted to monitor meningitis cases, which may facilitate the development of prevention and treatment strategies in India.
PubMed: 34589213
DOI: 10.1177/20499361211046453 -
Open Forum Infectious Diseases Oct 2022Tuberculosis is a leading cause of death among women of reproductive age. However, tuberculous meningitis, the most severe form of extrapulmonary tuberculosis, is rarely...
BACKGROUND
Tuberculosis is a leading cause of death among women of reproductive age. However, tuberculous meningitis, the most severe form of extrapulmonary tuberculosis, is rarely discussed in pregnancy despite this being a unique period of immune modulation that may predispose women to active disease.
METHODS
We identified and described cases of tuberculous meningitis among pregnant or postpartum women screened during meningitis clinical trials in Uganda from 2018 to 2022. We conducted a systematic literature review via PubMed/Medline and Embase for all English-language publications from 1970 to 10 July 2022, to identify additional cases.
RESULTS
We identified 8 cases of pregnancy-related tuberculous meningitis in Ugandan women living with human immunodeficiency virus (HIV) and 40 additional cases via systematic literature review (none HIV-positive). Of all combined cases, 50% (24/48) were diagnosed postpartum; 50% (24/48) had initial onset during pregnancy, of which 38% (9/24) had worsening of symptoms or disease relapse following pregnancy cessation. Diagnosis was missed or delayed in 33% (16/48) of cases. For those with known outcomes, maternal mortality was 23% (11/48) and fetal/neonatal mortality was 30% (13/44). Of maternal survivors, 30% (11/37) had residual neurologic deficits.
CONCLUSIONS
The true incidence of tuberculous meningitis in pregnancy or the postpartum period is unclear but likely underappreciated. To date, nearly all published cases have occurred in HIV-negative or otherwise immunocompetent women. Given the well-described physiological immunosuppression during pregnancy and subsequent reconstitution postpartum, physicians must be aware of tuberculous meningitis and pregnancy-related immune reconstitution inflammatory syndrome, especially in countries with a high burden of tuberculosis and in women living with HIV.
PubMed: 36267255
DOI: 10.1093/ofid/ofac513 -
Infectious Diseases and Therapy Nov 2023Streptococcus pneumoniae is the leading cause of meningitis, with a case fatality of up to about 50%. Children younger than 5 years are at greater risk for pneumococcal... (Review)
Review
INTRODUCTION
Streptococcus pneumoniae is the leading cause of meningitis, with a case fatality of up to about 50%. Children younger than 5 years are at greater risk for pneumococcal meningitis compared with other populations. It is of significant importance to provide a comprehensive understanding of the burden of pneumococcal meningitis among under-fives in the low pneumococcal conjugate vaccine (PCV) coverage period in China.
METHODS
A systematic review was conducted. We searched both English (PubMed, Ovid-EMBASE, Biosis, Web of Science, and Cochrane) and Chinese (CNKI, Wanfang, and ViP) databases for studies on bacterial meningitis in China published between January 1980 and July 2022. Ineligible studies were excluded based on study design and data integrity. Heterogeneity was assessed with I and estimates of bacterial meningitis morbidity and mortality were pooled using random-effects models. Subgroup analysis was conducted to trace the source of the heterogeneity and summarize average estimates.
RESULTS
A total of 13,082 studies were identified in the literature, and 56 studies were finally included for data analysis. The estimated incidence of pneumococcal meningitis was 2.10 cases per 100,000 children younger than 5 years each year (95% CI: 0.59-7.46), with a pooled case fatality rate of 24.59% (95%CI: 19.35-30.28%) in China. It was estimated that 1617.16 (95% CI: 454.35-5744.78) pneumococcal meningitis cases and 548.86 (95% CI: 474.80-627.62) deaths occurred among under-fives in China in 2020. Streptococcus pneumoniae played an important role in the etiology of confirmed bacterial meningitis cases, with a pooled proportion of 22.05% (95% CI: 17.83-26.27%). The most prevalent serotypes were 6B, 14, 19F, 19A, and 23F, which were preventable with a vaccine.
CONCLUSIONS
Pneumococcal meningitis remains one of the most important health problems among children younger than 5 years in China. Immunization programs should be promoted to avoid preventable cases and deaths.
PubMed: 37837523
DOI: 10.1007/s40121-023-00878-y -
Brain Communications 2024New treatments are needed to improve the prognosis of pneumococcal meningitis. We performed a systematic review on adjunctive treatments in animal models of pneumococcal... (Review)
Review
New treatments are needed to improve the prognosis of pneumococcal meningitis. We performed a systematic review on adjunctive treatments in animal models of pneumococcal meningitis in order to identify treatments with the most potential to progress to clinical trials. Studies testing therapy adjunctive to antibiotics in animal models of pneumococcal meningitis were included. A literature search was performed using Medline, Embase and Scopus for studies published from 1990 up to 17 February 2023. Two investigators screened studies for inclusion and independently extracted data. Treatment effect was assessed on the clinical parameters disease severity, hearing loss and cognitive impairment and the biological parameters inflammation, brain injury and bacterial load. Adjunctive treatments were evaluated by their effect on these outcomes and the quality, number and size of studies that investigated the treatments. Risk of bias was assessed with the SYRCLE risk of bias tool. A total of 58 of 2462 identified studies were included, which used 2703 experimental animals. Disease modelling was performed in rats (29 studies), rabbits (13 studies), mice (12 studies), gerbils (3 studies) or both rats and mice (1 study). Meningitis was induced by injection of into the subarachnoid space. Randomization of experimental groups was performed in 37 of 58 studies (64%) and 12 studies (12%) were investigator-blinded. Overall, 54 treatment regimens using 46 adjunctive drugs were evaluated: most commonly dexamethasone (16 studies), daptomycin (5 studies), complement component 5 (C5; 3 studies) antibody and Mn(III)tetrakis(4-benzoicacid)porphyrin chloride (MnTBAP; 3 studies). The most frequently evaluated outcome parameters were inflammation [32 studies (55%)] and brain injury [32 studies (55%)], followed by disease severity [30 studies (52%)], hearing loss [24 studies (41%)], bacterial load [18 studies (31%)] and cognitive impairment [9 studies (16%)]. Adjunctive therapy that improved clinical outcomes in multiple studies was dexamethasone (6 studies), C5 antibodies (3 studies) and daptomycin (3 studies). HMGB1 inhibitors, matrix metalloproteinase inhibitors, neurotrophins, antioxidants and paquinimod also improved clinical parameters but only in single or small studies. Evaluating the treatment effect of adjunctive therapy was complicated by study heterogeneity regarding the animal models used and outcomes reported. In conclusion, 24 of 54 treatment regimens (44%) tested improved clinically relevant outcomes in experimental pneumococcal meningitis but few were tested in multiple well-designed studies. The most promising new adjunctive treatments are with C5 antibodies or daptomycin, suggesting that these drugs could be tested in clinical trials.
PubMed: 38707710
DOI: 10.1093/braincomms/fcae131 -
Neurosurgery Dec 2022Chronic subdural hematoma (CSDH) is a common neurosurgical condition with a high risk of recurrence after treatment. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic subdural hematoma (CSDH) is a common neurosurgical condition with a high risk of recurrence after treatment.
OBJECTIVE
To assess and compare the risk of recurrence, morbidity, and mortality across various treatments for CSDH.
METHODS
A systematic review and meta-analysis was performed. PubMed/MEDLINE, EMBASE, SCOPUS, and Web of Science were searched from January 01, 2000, to July 07, 2021. The primary outcome was recurrence, and secondary outcomes were morbidity and mortality. Component network meta-analyses (CNMAs) were performed for surgical and medical treatments, assessing recurrence and morbidity. Incremental risk ratios (iRRs) with 95% CIs were estimated for each component.
RESULTS
In total, 12 526 citations were identified, and 455 studies with 103 645 cases were included. Recurrence occurred in 11 491/93 525 (10.8%, 95% CI 10.2-11.5, 418 studies) cases after surgery. The use of a postoperative drain (iRR 0.53, 95% CI 0.44-0.63) and middle meningeal artery embolization (iRR 0.19, 95% CI 0.05-0.83) reduced recurrence in the surgical CNMA. In the pharmacological CNMA, corticosteroids (iRR 0.47, 95% CI 0.36-0.61) and surgical intervention (iRR 0.11, 95% CI 0.07-0.15) were associated with lower risk. Corticosteroids were associated with increased morbidity (iRR 1.34, 95% CI 1.05-1.70). The risk of morbidity was equivalent across surgical treatments.
CONCLUSION
Recurrence after evacuation occurs in approximately 10% of cSDHs, and the various surgical interventions are approximately equivalent. Corticosteroids are associated with reduced recurrence but also increased morbidity. Drains reduce the risk of recurrence, but the position of drain (subdural vs subgaleal) did not influence recurrence. Middle meningeal artery embolization is a promising treatment warranting further evaluation in randomized trials.
Topics: Humans; Hematoma, Subdural, Chronic; Network Meta-Analysis; Treatment Outcome; Meningeal Arteries; Subdural Space; Drainage
PubMed: 36170165
DOI: 10.1227/neu.0000000000002144 -
Acta Neurochirurgica Oct 2023Meningiomas are the most common primary intracranial tumor. While the majority of meningiomas are benign, rarely they can metastasize extracranially. There is a need for...
BACKGROUND
Meningiomas are the most common primary intracranial tumor. While the majority of meningiomas are benign, rarely they can metastasize extracranially. There is a need for a more comprehensive review of these patients to improve our understanding of this rare phenomenon and its prevalence globally. Here we describe our institution's experience of patients presenting with metastatic meningiomas. We further perform a systematic review of the existing literature to explore common features of this rare manifestation of meningioma and review the efficacy of current treatments.
METHODS
We performed a retrospective clinical review of all adult patients with metastatic meningioma managed at our institution over the past 20 years, identifying 6 patients. We then performed a systematic review of cases of metastatic meningioma in the literature ranging from the years 1886 to 2022. A descriptive analysis was then conducted on the available data from 1979 onward, focusing on the grade and location of the primary tumor as well as the latency period to, and location of, the metastasis.
RESULTS
In total, we analyzed 155 cases. Fifty-four percent of patients initially presented with a primary meningioma located in the convexity. The most common site of metastasis was the lung. Risk factors associated with a shorter time to metastasis were male sex and a high initial grade of the tumor. Regarding treatment, the addition of chemotherapy was the most common adjunct to the standard management of surgery and radiotherapy. Despite an exhaustive review we were unable to identify effective treatments. The majority of published cases came from centers situated in high-income countries (84%) while only 16% came from lower- and middle-income countries.
CONCLUSIONS
Metastatic meningiomas pose a pertinent, and likely underestimated, clinical challenge within modern neurosurgery. To optimize management, timely identification of these patients is important. More research is needed to explore the mechanisms underlying these tumors to better guide the development of effective screening and management protocols. However, screening of each meningioma patient is not feasible, and at the heart of this challenge is the inability to control the primary disease. Ultimately, a consensus is needed as to how to correctly screen for and manage these patients; genomic and epigenomic approaches could hold the answer to finding druggable targets.
Topics: Adult; Female; Humans; Male; Brain Neoplasms; Meningeal Neoplasms; Meningioma; Retrospective Studies; Treatment Outcome
PubMed: 37491650
DOI: 10.1007/s00701-023-05687-3 -
Clinical Microbiology and Infection :... Mar 2023Streptococcus pneumoniae is a leading cause of bacterial meningitis worldwide. Conventional microbiological assays take several days and require the use of various drugs... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Streptococcus pneumoniae is a leading cause of bacterial meningitis worldwide. Conventional microbiological assays take several days and require the use of various drugs for empirical treatment. Rapid antigen tests in cerebrospinal fluid (CSF) may be useful to triage pneumococcal meningitis immediately.
OBJECTIVES
To elucidate whether rapid antigen tests in CSF are useful in the triage of pneumococcal meningitis.
METHODS
Data sourcesCochrane CENTRAL, MEDLINE, EMBASE, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov databases were searched. Study eligibility criteriaAll types of cohort studies except multiple-group studies, where the sensitivity and specificity of rapid antigen tests in CSF compared with CSF culture can be extracted. ParticipantsPatients with suspected meningitis. TestsRapid antigen tests in CSF. Reference standardsOne or more of the following: blood culture, CSF culture, and polymerase chain reaction in CSF. Assessment of risk of biasThe methodological quality of the included studies was assessed using QUADAS-2. Methods of data synthesisWe used a random-effects bivariate model for the meta-analysis. We conducted a subgroup analysis by dividing studies into types of antigen tests, adults and children, low-income and high-income countries, and with or without exposure to antibiotics before lumbar puncture.
RESULTS
Forty-four studies involving 14 791 participants were included. Most studies had a moderate-to-low methodological quality. Summary sensitivity and specificity were 99.5% (95% confidence interval (CI), 92.4-100%) and 98.2% (95% CI, 96.9-98.9%), respectively. Positive predictive values and negative predictive values at the median prevalence (4.2%) in the included studies were 70.8% (95% CI, 56.6-79.9%) and 100% (95% CI, 99.7-100%), respectively. The diagnostic accuracy was consistent across the various subgroups, except for slightly reduced sensitivity in high-income countries.
CONCLUSIONS
Rapid antigen tests in CSF would be useful in triaging pneumococcal meningitis. Further studies are warranted to investigate the clinical benefit of ruling out pneumococcal meningitis based on the results of rapid antigen tests.
Topics: Child; Adult; Humans; Meningitis, Pneumococcal; Streptococcus pneumoniae; Immunologic Tests; Cohort Studies; Sensitivity and Specificity
PubMed: 36503113
DOI: 10.1016/j.cmi.2022.12.002 -
Indian Journal of Medical Microbiology 2022Neisseria meningitidis is one of the most important causes of meningitis and pathogens-associated deaths in developing and developed countries. Effective anti-microbial... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neisseria meningitidis is one of the most important causes of meningitis and pathogens-associated deaths in developing and developed countries. Effective anti-microbial agents are pivotal to treat and control N. meningitidis infections. The aim of the present study was to systematically review published studies on the antibiotic resistance of N. meningitidis in the last 20 years (2000-2020) in the world.
METHODS
Published researches were identified through a literature search using reputable databases including PubMed, Scopus, and Web of Science. Finally, 24 studies were included for a random-effects model meta-analysis.
RESULTS
The overall resistance to most commonly used antibiotics such as ceftriaxone, cefotaxime, ciprofloxacin and rifampin was low, ranging from 1 to 3.4%. However, non-sensitivity to penicillin, as the first-line antibiotic against N. meningitidis, was higher (27.2%). Altogether, the resistance to the first-line antibiotics (except penicillin) is still low indicating these drugs are effective against meningococcal meningitis. We also found a significant gap between MIC and disk diffusion for evaluating resistance to antibiotics in which disk diffusion overestimate the resistance rate.
CONCLUSIONS
To properly management and prevent the spread of N. miningitidis isolates resistant antibiotics, it is necessary to monitor the pattern of antibiotic susceptibility regionally and globally using the MIC methods.
Topics: Anti-Bacterial Agents; Drug Resistance, Microbial; Humans; Meningococcal Infections; Microbial Sensitivity Tests; Neisseria meningitidis; Penicillins
PubMed: 35654713
DOI: 10.1016/j.ijmmb.2022.05.005 -
Neurocritical Care Dec 2016Due to increasing prevalence of intracranial device use and multidrug-resistant and nosocomial organisms, central nervous system (CNS) infections requiring treatment... (Review)
Review
Due to increasing prevalence of intracranial device use and multidrug-resistant and nosocomial organisms, central nervous system (CNS) infections requiring treatment with intraventricular (IVT) aminoglycosides are becoming increasingly common. This article systematically reviews IVT aminoglycoside literature in adults and integrates available evidence to serve as a practical reference for clinicians. Medline (1946 to December 2015), Embase (1974 to December 2015), PubMed (1966 to December 2015), Google, and Google Scholar were searched using the term aminoglycoside combined individually with the terms IVT, meningitis, shunt infection, ventriculitis, and cerebral spinal fluid. Eighteen articles were included. IVT aminoglycosides were assessed in meningitis, ventriculitis, intracranial device infections and neurosurgery prophylaxis. No serious adverse effects following IVT aminoglycoside were reported. Dosages ranged from IVT gentamicin 4-10 mg daily, IVT tobramycin 5-10 mg daily, and IVT amikacin 5-50 mg daily. Duration of therapy should be individualized; however, continuing IVT antibiotics for 3 days and up to 21 days after cerebrospinal fluid (CSF) sterilization has been reported in literature. Most studies included concomitant intravenous antibiotic use. Therapeutic drug monitoring (TDM) was reported in five studies, with varying timing of CSF concentrations obtained. No clear relationship between CSF levels and efficacy or toxicity was evident. Based on current literature, IVT aminoglycosides for the treatment of sensitive gram-negative meningitis, ventriculitis, and CNS device-associated infections appear safe and effective. Optimal dosing regimens are unclear. It is reasonable to initiate IVT aminoglycoside at lowest dose in combination with IV therapy and continuing post CSF sterilization. Preservative-free formulations should be utilized to minimize adverse drug reactions. TDM should not be routinely utilized but reserved for more complicated patients. Further pharmacokinetic and clinical trials of IVT aminoglycosides are necessary to fill current therapeutic gaps. Due to the relatively limited cases of IVT aminoglycoside utilization, prospective, randomized, controlled trials are likely not feasible, and clinicians will have to rely on data from non-randomized and/or retrospective studies.
Topics: Adult; Aminoglycosides; Central Nervous System Infections; Cross Infection; Humans; Injections, Intraventricular
PubMed: 27043949
DOI: 10.1007/s12028-016-0269-3