Diagnosis Of Meningitis Research Articles

Positive Predictive Value of Contrast-Enhanced Fluid-Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Imaging in Diagnosis of Meningitis Among Pediatrics Taking Cerebrospinal Fluid Analysis as Gold Standard

Positive Predictive Value of Contrast-Enhanced Fluid-Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Imaging in Diagnosis of Meningitis Among Pediatrics Taking Cerebrospinal Fluid Analysis as Gold Standard

Predictive performance of cerebrospinal fluid parameters for diagnosis of meningitis in infants: a cohort study

BackgroundThe gold standard for diagnosis of meningitis is the isolation of a pathogen from cerebrospinal fluid (CSF) by culture or PCR. However, treatment is routinely commenced based on CSF findings prior to microbiological results. This study determined the predictive value of CSF parameters for diagnosing bacterial and viral meningitis in young infants.MethodsMulticentre retrospective (2010–2020) cohort study of 1088 CSF results from infants aged 0–90 days. The predictive value of CSF parameters (white blood cell count (WCC), neutrophil, protein, glucose) was evaluated in 538 meningitis cases (39 bacterial, 499 viral) compared with controls with negative CSF microbiological testing and no prior antibiotics.ResultsFor bacterial meningitis, the sensitivity of the commonly used CSF WCC cut-off of 20×106/L for neonates, 15×106/L for infants 1–2 months old and 5×106/L for infants 2–3 months old was 89%, 91% and 86% and the specificity was 78%, 77% and 61%, respectively. CSF protein levels ≥1 g/L in neonates and ≥0.8 g/L in infants aged 1–3 month, or CSF neutrophils ≥2×106/L, independently increased the likelihood of bacterial meningitis (positive likelihood ratios ≥5 and ≥3, respectively). 3 of 39 cases of bacterial meningitis would have been missed using the commonly used WCC cut-offs alone. However, two would have been identified using CSF protein and neutrophil thresholds. All CSF parameters were poor at identifying viral meningitis.ConclusionA single CSF parameter cannot reliably diagnose bacterial meningitis. For identification of bacterial meningitis, elevation of CSF WCC, neutrophil count or protein levels above threshold values improves accuracy of diagnosis.

Utility of cell index in the diagnosis of healthcare-associated ventriculitis and meningitis: an analytical cross-sectional study

BackgroundThe diagnosis of healthcare-associated ventriculitis and meningitis (HCAVM) can be complex because multiple factors confound the interpretation of cerebrospinal fluid (CSF) tests. The cell index (CI) may help in the diagnosis of HCAVM. It does not incur additional medical cost and it avoids delays from the turnaround time of CSF cultures. It is derived by calculating the ratio of CSF white blood cell (WBC) and red blood cell (RBC) divided by the ratio of peripheral WBC and RBC. This study aimed to evaluate the diagnostic utility of this parameter.MethodsAn analytic, observational, cross-sectional study was conducted at the University of the Philippines – Philippine General Hospital. All admitted pediatric and adult patients from 2015 to 2022 who underwent external ventricular drain (EVD) insertion for hydrocephalus secondary to intracranial hemorrhage (ICH), acute ischemic stroke, intracranial neoplasms, traumatic brain injury, or congenital hydrocephalus were screened. Records of patients fulfilling the inclusion criteria were then reviewed.ResultsA total of 363 patients underwent EVD insertion from 2015 to 2022. Of these, 161 were included in the study. Two-thirds (66.5%) were adults ≥ 19 years old whereas the remaining were pediatric patients 1 to < 19 years old. There were no patients < 12 months old as they fulfilled at least one exclusion criteria. Forty-nine of them were later confirmed to have HCAVM based on the CDC/NHSN criteria. A CI cut-off of ≥ 1.21 gave a maximum sensitivity of 30.6% and specificity of 86.4%. Receiver operating characteristic area under the curve (AUC-ROC) analysis was 0.585. Subgroup analysis by age showed sensitivity of 52.9% in the pediatric age group and 3.13% in adults. Subgroup analysis by neurologic indication showed sensitivity of 27.6% for ICH and 35.0% for neoplasms. Subsequent AUC-ROC analyses, however, showed that CI failed to adequately diagnose HCAVM in these subgroups.ConclusionsIn our population of neurologic patients who underwent EVD insertion, the cell index is not a reliable parameter in the diagnosis of HCAVM.

The challenge of etiologic diagnosis of subacute and chronic meningitis: an analysis of 183 patients.

Subacute and chronic meningitis (SCM) presents significant diagnostic challenges, with numerous infectious and non-infectious inflammatory causes. This study examined patients aged 16 and older with SCM admitted to referral centers for neuroinfections and neuroinflammations in Mashhad, Iran, between March 2015 and October 2022. Among 183 episodes, tuberculous meningitis was the most common infectious cause (46.5%), followed by Brucella meningitis (24.6%). The cause of SCM was definitively proven in 40.4%, presumptive in 35.0%, and unknown in 24.6% of cases. In-hospital mortality was 14.4%, and 30.5% of survivors experienced unfavorable outcomes (Glasgow Outcome Scale 2-4). Patients with unknown causes had a significantly higher risk of death compared to those with presumptive or proven diagnoses (risk ratio 4.18). This study emphasizes the diagnostic difficulties of SCM, with one-quarter of cases remaining undiagnosed and over one-third having only a presumptive diagnosis. Improving diagnostic methods could potentially enhance prognosis and reduce mortality.

Systemic Lupus Erythematosus, An Unusual Presentation: A Case Report In Azal Hospital, Sana’a, Yemen

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by various clinical presentations and potential involvement of multiple organ systems; it exhibits a significant female predominance, with a peak incidence of middle-aged individuals. In this article, we report a case of a 19 years old female patient who presented with fever, headache, fatigue and neck stiffness. Initial investigations revealed a normal white blood cell count (WBC) with neutrophilia, leading to a diagnosis of bacterial meningitis. The patient responded to antibiotic and analgesic treatment. However, subsequent development of arthritis and skin lesions raised suspicion of systemic lupus erythematosus, which was confirmed by positive anti-dsDNA and antinuclear antibody (ANA) tests.

A-140 Reducing cell count bias with the GloCyte® Automated Cell Counter for CSF: an observational study at Loyola University Medical Center

Abstract Background Accurate STAT cerebrospinal fluid (CSF) cell counts are critical in supporting diagnoses of meningitis, malignancy, demyelinating disease, and hemorrhage. Limitations of automated analyzers to achieve acceptable linearity for the clinically relevant range has maintained manual CSF cell counting as the preferred method. Manual cell counting, performed with a hemocytometer and bright field microscope, is time-consuming, requires specialized skills and depends on human interpretation. This subjectivity inherently introduces the potential for non-random error in the enumeration of both total nucleated cells (TNC) and red blood cells in CSF by manual methods. The purpose of this study was to evaluate and compare the level of bias inherent in manual determination (TNC) in CSF as compared to the GloCyte Automated Cell Counter. Methods Result bias data for CSF specimens processed in the hematology lab at Loyola University Medical Center, a quaternary care 547-bed academic medical center in Maywood, IL, was analyzed for manual cell counting using a Neubauer-improved hemocytometer and GloCyte, an FDA-cleared cell counting device employing fluorescence technology to automate RBC and TNC counts in under 5 minutes, with linearity down to 0 cells/µL. Result bias was determined by defining the “expected result” for both GloCyte and hemocytometer as the initial cell count determined at a 1:5 dilution of a freshly-collected CSF sample and calculating the expected cell count for subsequent serial dilutions of 1:10, 1:20, 1:50, 1:100 for each method. The actual TNC count and the disparity of the actual result from the expected result was recorded as bias. Results Data are summarized below in the Table, and indicate a lower bias for GloCyte compared to manual counts across the range of dilutions. Conclusions This study demonstrates that GloCyte can be implemented as a means of effectively mitigating the reporting bias of CSF TNC counts performed with a Neubauer-improved hemocytometer.

The Relationship between the Classic Triad of Meningitis and Types of Meningitis

Meningitis is an inflammatory disease of the meninges caused by infection and non-infection. Based on WHO data for 2023, the CFR (Case Fatality Rate) for meningitis is 5.88%. In 2016 at the Southeast Asian level, Indonesia became the country with the highest mortality rate caused by meningitis. The classic triad of meningitis can assist in the early diagnosis of meningitis so that early management can be carried out to reduce mortality and morbidity if a cerebrospinal fluid examination is not possible immediately. Therefore, a study was conducted to determine the characteristics of meningitis patients, prevalence, and the relationship between the classic triad of meningitis and the incidence of infectious and non-infectious meningitis at Dr. Sardjito General Hospital Yogyakarta in 2017-2021. This study uses a cross-sectional method. The data taken is secondary data from 118 medical records of patients who have been treated. From the results, it was obtained that the highest characteristics and distribution were the age category 0-5 years (27.1%), male sex (51.7%), the most domicile outside DIY (54.2%), no/not yet school (36.4%) not/not yet working (38.1%), bacterial meningitis (39.0%), fever (89.8%), neck stiffness (78.8%). There is a significant relationship between the classic triad of meningitis and the type of meningitis (p-value 0.000). Among the three triads, it turned out that there was a solid relationship between the classic triad of meningitis and the type of infectious meningitis as indicated p-value by neck stiffness 0.000, fever 0.000, and headache 0.000.

Significance of relative and absolute content of blood lymphocyte subopopulations for differential diagnosis of viral and bacterial meningitis in children

The search for markers of early etiological verification of meningitis is an urgent task for clinical laboratory diagnostics.Objective of the study is to determine the significance of relative and absolute content of blood lymphocyte subpopulations for early differential diagnosis of viral and bacterial meningitis in children.Materials and methods. There was performed a clinical and laboratory examination of 61 children, 37 of them were diagnosed with viral meningitis, and 24 ones – with bacterial purulent meningitis. The control group included 15 healthy children. The relative and absolute content of the main subpopulations (T-lymphocytes: T-helpers (Th), cytotoxic T-lymphocytes (CTL), NK, B-cells) and small subpopulations (NKT, DNT- and DPT-lymphocytes, CD3+CD8br, CD3+CD8dim, CD3-CD8+NK) of lymphocytes was assessed by flow cytometry. Statistical analysis of the data was carried out.Results. The decrease of relative and absolute content of all studied subpopulations was identified during an acute period of bacterial purulent meningitis, in comparison with the control group, with the exception of B-lymphocytes, the number of them was increased. Absolute content of all subpopulations was reduced in case of viral meningitis compared with the control group, the relative content did not have any significant differences, with the exception of an increase in the relative content of B-lymphocytes. Calculation of diagnostic sensitivity and specificity revealed the effectiveness of identification of both relative and absolute content of lymphocyte subpopulations for differential diagnosis of viral or bacterial meningitis. Identification of B-lymphocytes, NKT, CD3+CD8dim in the blood had the highest diagnostic efficiency (area under the ROC curve (AUC) ranging from 0,9 to 1).Conclusion. Assessment of relative and absolute content of blood lymphocyte subpopulations is an effective tool for laboratory differential diagnosis of viral and bacterial meningitis and can be used as an early differential diagnostic criterion, especially in case of impossibility to analyze the composition of cerebrospinal fluid.

Laboratory diagnosis of cryptococcal meningitis in an HIV-infected patient

Laboratory diagnosis of cryptococcal meningitis in an HIV-infected patient

Paroxysmal Sympathetic Hyperactivity in Childhood Tuberculous Meningitis: A New Association.

We sought to estimate the prevalence and clinical characteristics of paroxysmal sympathetic hyperactivity (PSH) in childhood tuberculous meningitis. Hospital records of children (6 months to 14 years) with tuberculous meningitis were retrospectively analyzed from September 2019 through January 2022. In September 2019, the first case of paroxysmal sympathetic hyperactivity in tuberculous meningitis was identified in our division. Since then, all admitted children with tuberculous meningitis have been screened for paroxysmal sympathetic hyperactivity using the Paroxysmal Sympathetic Hyperactivity Assessment Measure (PSH-AM). Paroxysmal sympathetic hyperactivity is suspected when any of the following are present: recurrence of fever after initial defervescence, episodic posturing, dystonia, or unexplained tachycardia. Outcome at 3 months was prospectively scored according to the Pediatric Cerebral Performance Category score. Forty-one hospital records of children with tuberculous meningitis were analyzed, and 6 of them had paroxysmal sympathetic hyperactivity (probable paroxysmal sympathetic hyperactivity, 5/6; possible paroxysmal sympathetic hyperactivity, 1/6). Paroxysmal sympathetic hyperactivity appeared after a mean duration of 17 weeks (range: 12-25 weeks) from the diagnosis of tuberculous meningitis in 4 of 6 children and at 4 weeks in 2 of 6 children. Children with tuberculous meningitis who developed paroxysmal sympathetic hyperactivity were younger (median age: 5 years) compared with the nonparoxysmal sympathetic hyperactivity tuberculous meningitis cohort (median age: 10 years). A high proportion of children who developed paroxysmal sympathetic hyperactivity had hydrocephalus at presentation (5 of 6 [83.3%] vs 12 of 35 [34.3%], P = .035). Hospital stay was significantly prolonged in children with probable paroxysmal sympathetic hyperactivity (mean: 71.2 ± 26.8 days) compared with tuberculous meningitis without paroxysmal sympathetic hyperactivity (mean: 20.8 ± 11.6 days; P < .0001). Paroxysmal sympathetic hyperactivity is a late complication of tuberculous meningitis observed in 14.6% cases and should be anticipated in children with reappearance of fever or neurologic worsening without any apparent cause.

Diagnosis and management of bacterial meningitis in adult Sudanese patients: a six years hospital based, retrospective, cross-sectional study

PurposeTo evaluate the diagnosis and management of bacterial meningitis in adult Sudanese patients in accordance with the Infectious Diseases Society of America (IDSA) guidelines for bacterial meningitis management.Patients and methodsA cross-sectional, retrospective study design was used to recruit all patients aged > 18 years who were diagnosed with or suspected of having bacterial meningitis and admitted to Wad Medani Teaching Hospital, Gezira State, Sudan, between January 2017 and October 2022.ResultsIn total, 201 patients were included in the analysis. The mean age of the participants was 44.1 ± 21.4 years, and 107 (53.2%) were male. Community-acquired bacterial meningitis accounted for 193 (96%) of the studied patients, and only 8 (4%) of the patients had healthcare-associated meningitis. Neuroimaging was utilized appropriately in 148 (73.6%) patients, blood cultures were not performed entirely, and lumbar puncture was seldom performed in 1 (0.5%) patient. Corticosteroids were appropriately administered to 65 (32.3%) patients, and antibiotics were administered appropriately to only 5 (2.5%) patients. Ceftriaxone 185 (76.1%) was the most frequently utilized antibiotic, followed by vancomycin 23 (9.5%). In terms of overall adherence, this study demonstrated that the IDSA guidelines were not followed at all in the treatment of patients with suspected bacterial meningitis.ConclusionThe results of this study contradict the IDSA guidelines for the standard of care for bacterial meningitis. Antibiotic regimens are often incorrect, corticosteroids are administered appropriately in approximately one-third of patients, and neuroimaging is reasonably utilized. This study raises attention to several important issues regarding the diagnosis of bacterial meningitis, including the lack of confirming microbiological tests and the reliance of the diagnosis primarily on CT and clinical examination.

Cerebrospinal fluid-induced stable and reproducible SERS sensing for various meningitis discrimination assisted with machine learning

Cerebrospinal fluid (CSF)-based pathogen or biochemical testing is the standard approach for clinical diagnosis of various meningitis. However, misdiagnosis and missed diagnosis always occur due to the shortages of unusual clinical manifestations and time-consuming shortcomings, low sensitivity, and poor specificity. Here, for the first time, we propose a simple and reliable CSF-induced SERS platform assisted with machine learning (ML) for the diagnosis and identification of various meningitis. Stable and reproducible SERS spectra are obtained within 30 s by simply mixing the colloidal silver nanoparticles (Ag NPs) with CSF sample, and the relative standard deviation of signal intensity is achieved as low as 2.1%. In contrast to conventional salt agglomeration agent-induced irreversible aggregation for achieving Raman enhancement, a homogeneous and dispersed colloidal solution is observed within 1 h for the mixture of Ag NPs/CSF (containing 110–140 mM chloride), contributing to excellent SERS stability and reproducibility. In addition, the interaction processes and potential enhancement mechanisms of different Ag colloids-based SERS detection induced by CSF sample or conventional NaCl agglomeration agents are studied in detail through in-situ UV–vis absorption spectra, SERS analysis, SEM and optical imaging. Finally, an ML-assisted meningitis classification model is established based on the spectral feature fusion of characteristic peaks and baseline. By using an optimized KNN algorithm, the classification accuracy of autoimmune encephalitis, novel cryptococcal meningitis, viral meningitis, or tuberculous meningitis could be reached 99%, while an accuracy value of 68.74% is achieved for baseline-corrected spectral data. The CSF-induced SERS detection has the potential to provide a new type of liquid biopsy approach in the fields of diagnosis and early detection of various cerebral ailments.

Update on diagnosis and treatment of fungal meningitis: lessons from recent outbreaks.

Recently, fungal meningitis outbreaks have occurred in association with neuraxial and epidural anesthesia in immunocompetent patients. Herein, we describe the course of those outbreaks, their diagnosis, treatment, prognosis, and lessons learned. Two outbreaks of Fusarium solani meningitis during 2022-2023 were associated with epidural anesthesia in two distant cities in Mexico (Durango and Matamoros). The initial etiological agent identification was delayed due to insensitivity of cultures. A Fusarium solani qPCR was validated and positive in 38% cerebrospinal fluid (CSF) samples from Durango, while BD-Glucan allowed early diagnosis of the index case in Matamoros. Antifungal treatment with voriconazole and liposomal amphotericin B (L-AmB) was recommended. Overall mortality was 51%. Once the cause was confirmed, some patients received fosmanogepix. Fungal meningitis outbreaks due to filamentous fungi are usually associated with direct epidural inoculation. They result in severe presentations and high mortality. Early diagnosis should be suspected, BD-Glucan CSF testing screening is recommended. Aggressive antifungal treatment based on antifungal susceptibility testing should be administered as early as possible. The advent of molecular diagnostic methods and new antifungal drugs may allow for timely diagnosis and treatment, increasing the chances of survival.

The Impact of GeneXpert Cerebrospinal Fluid Testing on Tuberculous Meningitis Diagnosis in Routine Care in Botswana

Abstract Background Tuberculous meningitis (TBM) disproportionately impacts high–HIV prevalence, resource-limited settings where diagnosis is challenging. The GeneXpert platform has utility in TBM diagnosis, but uptake remains limited. In Botswana, before the introduction of GeneXpert, tuberculosis (TB) testing was only available through mycobacterial culture at the National TB Reference Laboratory. Data describing routine use of Xpert MTB/RIF for cerebrospinal fluid (CSF) testing in resource-limited settings are scarce. Methods Electronic records for patients with CSF tested in government facilities in Botswana between 2016 and 2022 were obtained from a central online repository as part of ongoing national meningitis surveillance. Samples were excluded from 1 site where Xpert MTB/RIF is performed universally. The proportion receiving TB-specific investigation on CSF and the number positive for Mycobacterium tuberculosis following increased Xpert MTB/RIF capacity were determined. Results The proportion of CSF samples receiving TB-specific investigation increased from 4.5% (58/1288) in 2016 to 29.0% (201/693) in 2022, primarily due to increased analysis with Xpert MTB/RIF from 0.9% (11/1288) to 23.2% (161/693). There was an overall decline in the annual number of CSF samples analyzed, but the proportion with microbiologically confirmed TBM increased from 0.4% to 1.2%. The proportion of samples tested for TB that were collected from health care facilities &amp;gt;100 km from the National TB Reference Laboratory increased with Xpert MTB/RIF rollout from 65.9% (87/132) to 78.0% (494/633). Conclusions In Botswana, access to TB culture is challenging in remote populations; more accessible near-patient testing using Xpert MTB/RIF increased the number of patients receiving TB-specific testing on CSF and the number of confirmed TBM cases.

Sensitivity and Specificity of Jolt Accentuation Maneuver in Diagnosis of Acute Meningitis

Background: Acute meningitis is a potentially fatal illness that necessitates immediate identification and medical intervention. The Jolt Accentuation Maneuver (JAM) is a straightforward and non-invasive diagnostic test that can help in diagnosis of acute meningitis. Objectives: This study assessed the accuracy of JAM in detecting acute meningitis by evaluating its sensitivity and specificity. Methods: The study was done at Pak Emirate Military Hospital, Rawalpindi, from January 2024 to June 2024, using prospective observational method. 280 patients with symptoms indicative of meningitis were included in the study. Every patient received JAM procedure, followed by an examination of CSF, which was used as the definitive method for diagnosis. Results: The study group had average age of 35.2 years and was almost equally divided between males (50.7%) and females (49.3%). The prevalent symptoms consisted of headache (97.1%), fever (92.9%) and neck stiffness (82.1%). The JAM test demonstrated sensitivity of 88.9% (p&lt;0.001) and specificity of 60.0% (p&lt;0.05). The positive predictive value (PPV) was 80.0% (p&lt;0.05) and negative predictive value (NPV) was 75.0% (p&lt;0.05). The overall accuracy of the data was 82.1% (p&lt;0.001) indicating statistical significance. The study of ROC curve revealed an area under the curve of 0.90, indicating a high level of diagnostic accuracy. Conclusions: JAM is a diagnostic test for acute meningitis that is quite sensitive and has a decent level of specificity. Due to its high sensitivity, it is highly effective tool for initial screening, particularly in emergency circumstances. Nevertheless, because of its moderate specificity, it is necessary to confirm positive JAM results with other diagnostic testing. Incorporating JAM into clinical practice can expedite diagnosis and prompt treatment, potentially enhancing patient outcomes. Keywords: Acute meningitis, Diagnosis, Jolt Accentuation Maneuver, Sensitivity, Specificity.

Human Herpesvirus 6-A Rare Aetiologic Agent for CNS Infections in Immunocompetent Individuals or an Underestimation?

Background: Human herpesvirus 6 (HHV-6) is considered a ubiquitous virus, with many countries reporting a seroprevalence of more than 80-90% among the general population. However, this virus is unique among herpesviruses in its ability to integrate into the genetic material of the host's cells. Thus, there are three ways by which HHV-6 can cause an active infection-primary infection, reactivation of a latent acquired infection, or activation of iciHHV-6 (inherited chromosomally integrated HHV-6). Whole blood quantitative polymerase chain reaction (qPCR) is very useful in distinguishing between iciHHV-6 and primary infection/reactivation. Our aim is to assess the role of HHV-6 in the aetiology of central nervous system (CNS) infections in adults and children, to describe all HHV-6-positive cases in an attempt to determine the susceptible population and to identify potential risk factors that can be linked to HHV-6 meningoencephalitis. Methods: We performed a retrospective study involving patients that were admitted to Prof. Dr. Matei Bals National Institute of Infectious Diseases, Bucharest, Romania, with a diagnosis of meningitis or encephalitis. We only selected the clinical records of patients that had a multiplex PCR Biofire® FilmArray® meningitis/encephalitis panel. Results: We report a 5% HHV-6 positivity in the cerebrospinal fluid (CSF) of patients with CNS infections tested with a commercial multiplex PCR M/E (meningitis/encephalitis) panel. Additionally, 2% to 4% of the total study population (n = 100) had active HHV-6 infections, which denotes 40 to 80% of the HHV-6-positive samples. We did not observe any statistically significant correlation between HHV-6 positivity in the CSF and variables such as age, sex, or comorbidities, including obesity, diabetes, hypertension, immunosuppression, or oncologic disease. Therefore, no risk factors could be linked with HHV-6 positivity in the CSF. Conclusions: although multiplex qualitative PCR is highly useful for providing rapid results and identifying nearly every pathogen that can cause meningitis/encephalitis, we have to be aware of this type of test's limitations. All patients with HHV-6 detectable in their CSF via a multiplex PCR test should also undergo qPCR testing from both CSF and blood to prevent over-diagnosing HHV-6 CNS infections, to avoid unnecessary antiviral treatments, and ensure the accurate identification of the true diagnosis.

Sudden death in a newborn from cerebral venous sinus thrombosis resulting from meningitis.

Septic cerebral venous sinus thrombosis is a rare but often fatal complication caused by bacterial meningitis and paranasal sinusitis.We report a particular case of the sudden and unexpected death of a six-day-old infant from unrecognised acute meningitis that caused a thrombotic occlusion of the venous sinuses (with the particular involvement of the torcular Herophili at the confluence of sinuses) resulting in subdural haemorrhage.This case report alerts paediatricians and neonatologists to the importance of promptly considering a possible diagnosis of meningitis without delay to avoid the fatal complications described here. As in all cases of sudden infant death our case study underlines the need for a thorough autopsy, accompanied by histological analysis, in order to identify the causes of the underlying pathological mechanisms causing death and to ensure an adequate differential diagnosis.

A DAMP-Based Assay for Rapid and Affordable Diagnosis of Bacterial Meningitis Agents: Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae.

The rapid and accurate diagnosis of meningitis is critical for preventing severe complications and fatalities. This study addresses the need for accessible diagnostics in the absence of specialized equipment by developing a novel diagnostic assay. The assay utilizes dual-priming isothermal amplification (DAMP) with unique internal primers to significantly reduce non-specificity. For fluorescence detection, the dye was selected among Brilliant Green, Thioflavin T, and dsGreen. Brilliant Green is preferred for this assay due to its availability, high fluorescence level, and optimal sample-to-background (S/B) ratio. The assay was developed for the detection of the primary causative agents of meningitis (Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae), and tested on clinical samples. The developed method demonstrated high specificity, no false positives, sensitivity comparable to that of loop-mediated isothermal amplification (LAMP), and a high S/B ratio. This versatile assay can be utilized as a standalone test or an integrated assay into point-of-care systems for rapid and reliable pathogen detection.

Clinical application and evaluation of metagenomic next-generation sequencing in pathogen detection for suspected central nervous system infections

Central nervous system Infections (CNSIs) is a disease characterized by complex pathogens, rapid disease progression, high mortality rate and high disability rate. Here, we evaluated the clinical value of metagenomic next generation sequencing (mNGS) in the diagnosis of central nervous system infections and explored the factors affecting the results of mNGS. We conducted a retrospective study to compare mNGS with conventional methods including culture, smear and etc. 111 suspected CNS infectious patients were enrolled in this study, and clinical data were recorded. Chi-square test were used to evaluate independent binomial variables, taking p < 0.05 as statistically significant threshold. Of the 111 enrolled cases, 57.7% (64/111) were diagnosed with central nervous system infections. From these cases, mNGS identified 39.6% (44/111) true-positive cases, 7.2% (8/111) false-positive case, 35.1% (39/111) true-negative cases, and 18.0% (20/111) false-negative cases. The sensitivity and specificity of mNGS were 68.7% (44/64) and 82.9% (39/47), respectively. Compared with culture, mNGS provided a higher pathogen detection rate in CNSIs patients (68.7% (44/64) vs. 26.5% (17/64), p < 0.0001). Compared to conventional methods, positive percent agreement and negative percent agreement was 84.60% (44/52) and 66.1% (39/59) separately. At a species-specific read number (SSRN) ≥ 2, mNGS performance in the diagnosis of definite viral encephalitis and/or meningitis was optimal (area under the curve [AUC] 0.758, 95% confidence interval [CI] 0.663–0.854). In bacterial CNSIs patients with significant CSF abnormalities (CSF WBC > 300*106/L), the positive rate of CSF mNGS is higher. To sum up, conventional microbiologic testing is insufficient to detect all neuroinvasive pathogens, and mNGS exhibited satisfactory diagnostic performance in CNSIs and with an overall detection rate higher than culture (p < 0.0001).

High-Resolution Ultrasound Platform for Infant Meningitis Detection: An In Vitro Demonstration.

Infant meningitis remains a severe burden on global health, particularly for young infants. Traditional ultrasound imaging techniques are limited in spatial resolution to visualize white blood cells (WBCs) in the cerebrospinal fluid (CSF), which is considered a well-established marker for meningitis detection. This work presents a novel platform that uses high-resolution ultrasound to detect the backscatter signals from microscopic CSF WBCs through the anterior fontanelle of neonates and young infants. The whole system was built around a custom probe that allows for a 20 MHz focused transducer to be mechanically controlled to map the area of interest in the CSF. Data processing can be performed internally in the device without the need to extract the images for further analysis. The in vitro feasibility of the proposed solution was evaluated in imaging 7 μm particle suspensions at different concentrations relevant to meningitis diagnosis ranging from 7- to 646-particles (pp)/μL. The experimental tests were conducted from a simple setup using a sample container to a more realistic setup based on an anatomical phantom of the neonatal head. The results show high-quality images, where 7 μm particles can be resolved for the different concentrations.