Diagnostic prediction models for bacterial meningitis in children with a suspected central nervous system infection: a systematic review and prospective validation study.

OBJECTIVES: Diagnostic prediction models exist to assess the probability of bacterial meningitis (BM) in paediatric patients with suspected meningitis. To evaluate the diagnostic accuracy of these models in a broad population of children suspected of a central nervous system (CNS) infection, we performed external validation. METHODS: We performed a systematic literature review in Medline to identify articles on the development, refinement or validation of a prediction model for BM, and validated these models in a prospective cohort of children aged 0-18 years old suspected of a CNS infection. PRIMARY AND SECONDARY OUTCOME MEASURES: We calculated sensitivity, specificity, predictive values, the area under the receiver operating characteristic curve (AUC) and evaluated calibration of the models for diagnosis of BM. RESULTS: In total, 23 prediction models were validated in a cohort of 450 patients suspected of a CNS infection included between 2012 and 2015. In 75 patients (17%), the final diagnosis was a CNS infection including 30 with BM (7%). AUCs ranged from 0.69 to 0.94 (median 0.83, interquartile range [IQR] 0.79-0.87) overall, from 0.74 to 0.96 (median 0.89, IQR 0.82-0.92) in children aged ≥28 days and from 0.58 to 0.91 (median 0.79, IQR 0.75-0.82) in neonates. CONCLUSIONS: Prediction models show good to excellent test characteristics for excluding BM in children and can be of help in the diagnostic workup of paediatric patients with a suspected CNS infection, but cannot replace a thorough history, physical examination and ancillary testing.

[Evaluation of the Bio-Speedy Meningitis/Encephalitis Panel in the Diagnosis of Central Nervous System Infections]. / Merkezi Sinir Sistemi Enfeksiyonlarinin Tanisinda Bio-Speedy Menenjit/Ensefalit Panelinin Degerlendirilmesi.

Infections of the central nervous system (CNS) can lead to severe outcomes if not accurately diagnosed and treated. The broad spectrum of pathogens involved in CNS infections can make diagnosis challenging. Polymerase chain reaction (PCR) -based multiplex molecular diagnostic panels can rapidly and simultaneously detect multiple neuropathogens in cerebrospinal fluid (CSF). This study was aimed to assess the Bio-Speedy Meningitis/Encephalitis RT-PCR MX-17 panel (Bioeksen, Istanbul, Türkiye), a novel multiplex PCR test, in diagnosing CNS infections. The panel can detect a range of pathogens, including Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus pneumoniae, Streptococcus agalactiae, enterovirus (EV), herpes simplex virus (HSV) 1 and 2, HHV-6, HHV-7, HHV-8, human parechovirus (HPeV), varicella zoster virus (VZV), cytomegalovirus (CMV) and Cryptococcus gatti/neoformans in CSF samples. This retrospective study included 128 CSF samples from 128 patients sent to Bursa Uludag University Health Application and Research Center Microbiology Laboratory between June 2022 and July 2023 to search for CNS infectious agents. Patient clinical, radiological and laboratory data were collected from the Hospital Information Record System (HIRS). Bacterial pathogens were identified through culture, while viral pathogens were detected in CSF samples using the Fast Track Diagnostics (FTD) multiplex RT-PCR panel (Fast Track Diagnostics Ltd., Luxembourg) for HSV-1, HSV-2, VZV, EV, mumps virus and HPeV. The stored CSF samples were then tested using the BioSpeedy panel and the results were compared with those of the culture and the FTD panel. Pathogens that were detected were considered positive if they were consistent with the patient's symptoms and CSF characteristics according to infectious disease and pediatric infectious disease specialists. Pathogens detected but not supported by the patient's symptoms and CSF characteristics were classified as uncertain clinical relevance (UCR). Out of the 128 patients tested for CNS infectious agents, 44 (34.4%) were diagnosed with a CNS infection. The overall pathogen detection rate with all methods was 43.2% (19/44). The Bio-Speedy panel identified pathogens in 29.5% (13/44) of the patients, followed by the FTD panel (20.5%, 9/44) and culture (9.1%, 4/44). Four bacteria were identified with culture, three of which were also detected by the Bio-Speedy panel. Additionally, six bacteria were identified with Bio-Speedy panel, that were not identified by culture. The FTD panel identified nine viruses, four of which were also identified by Bio-Speedy. In total, the Bio-Speedy panel detected 13 of the 19 positive pathogens (nine bacteria and four viruses: [S.pneumoniae (n= 3), VZV (n= 3), N.meningitidis (n= 2), H.influenzae (n= 2), L.monocytogenes (n= 1), E.coli (n= 1) ve EV (n= 1)]. However, the Bio-Speedy panel identified 15 pathogens [S.pneumoniae (n= 1), E.coli (n= 1), C.gatti/neoformans (n= 1), CMV (n= 8), HHV-6 (n= 3) ve HHV-7 (n= 1)] considered as UCR. The Bio-Speedy identified the causative pathogens in the highest percentage (29.5%) of patients with confirmed CNS infections. Nevertheless, test results should be interpreted based on patient characteristics to ensure appropriate patient management. Using multiple methods and multiplex tests may improve diagnostic accuracy for CNS infections.

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).

Metagenomic next-generation sequencing of cerebrospinal fluid reveals etiological and microbiological features in patients with various central nervous system infections.

The application of metagenomic next-generation sequencing (mNGS) in pathogens detection of cerebrospinal fluid (CSF) is limited because clinical, microbiological, and biological information are not well connected. We analyzed the 428 enrolled patients' clinical features, pathogens diagnostic efficiency of mNGS in CSF, microbial community structure and composition in CSF, and correlation of microbial and clinical biomarkers in CSF. General characteristics were unspecific but helpful in formulating a differential diagnosis. CSF mNGS has a higher detection rate (34.6%) compared to traditional methods (5.4%). mNGS detection rate was higher when the time from onset to CSF collection was ≤20 days, the CSF leukocytes count was >200 × 106/L, the CSF protein concentration was >1.3 g/L, or CSF glucose concentration was ≤2.5 mmol/L in non-postoperative bacterial CNS infections (CNSi). CSF was not strictly a sterile environment, and the potential pathogens may contribute to the dysbiosis of CSF microbiome. Furthermore, clinical biomarkers were significantly relevant to CNS pathogens. Clinical data are helpful in choosing a proper opportunity to obtain an accurate result of mNGS, and can speculate whether the mNGS results are correct or not. Our study is a pioneering study exploring the CSF microbiome in different CNSIs.

Targeted metabolomics identifies accurate CSF metabolite biomarkers for the differentiation between COVID-19 with neurological involvement and CNS infections with neurotropic viral pathogens.

BACKGROUND: COVID-19 is primarily considered a respiratory tract infection, but it can also affect the central nervous system (CNS), which can result in long-term sequelae. In contrast to CNS infections by classic neurotropic viruses, SARS-CoV-2 is usually not detected in cerebrospinal fluid (CSF) from patients with COVID-19 with neurological involvement (neuro-COVID), suggesting fundamental differences in pathogenesis. METHODS: To assess differences in CNS metabolism in neuro-COVID compared to CNS infections with classic neurotropic viruses, we applied a targeted metabolomic analysis of 630 metabolites to CSF from patients with (i) COVID-19 with neurological involvement [n = 16, comprising acute (n = 13) and post-COVID-19 (n = 3)], (ii) viral meningitis, encephalitis, or myelitis (n = 10) due to herpes simplex virus (n = 2), varicella zoster virus (n = 6), enterovirus (n = 1) and tick-borne encephalitis virus (n = 1), and (iii) aseptic neuroinflammation (meningitis, encephalitis, or myelitis) of unknown etiology (n = 21) as additional disease controls. RESULTS: Standard CSF parameters indicated absent or low neuroinflammation in neuro-COVID. Indeed, CSF cell count was low in neuro-COVID (median 1 cell/µL, range 0-12) and discriminated it accurately from viral CNS infections (AUC = 0.99) and aseptic neuroinflammation (AUC = 0.98). 32 CSF metabolites passed quality assessment and were included in the analysis. Concentrations of differentially abundant (fold change ≥|1.5|, FDR ≤ 0.05) metabolites were both higher (9 and 5 metabolites) and lower (2 metabolites) in neuro-COVID than in the other two groups. Concentrations of citrulline, ceramide (d18:1/18:0), and methionine were most significantly elevated in neuro-COVID. Remarkably, triglyceride TG(20:1_32:3) was much lower (mean fold change = 0.09 and 0.11) in neuro-COVID than in all viral CNS infections and most aseptic neuroinflammation samples, identifying it as highly accurate biomarker with AUC = 1 and 0.93, respectively. Across all samples, TG(20:1_32:3) concentration correlated only moderately with CSF cell count (ρ = 0.65), protein concentration (ρ = 0.64), and Q-albumin (ρ = 0.48), suggesting that its low levels in neuro-COVID CSF are only partially explained by less pronounced neuroinflammation. CONCLUSIONS: The results suggest that CNS metabolite responses in neuro-COVID differ fundamentally from viral CNS infections and aseptic neuroinflammation and may be used to discover accurate diagnostic biomarkers in CSF and to gain insights into differences in pathophysiology between neuro-COVID, viral CNS infections and aseptic neuroinflammation.

Clinical Metagenomic Next-Generation Sequencing for Diagnosis of Central Nervous System Infections: Advances and Challenges.

Central nervous system (CNS) infections carry a substantial burden of morbidity and mortality worldwide, and accurate and timely diagnosis is required to optimize management. Metagenomic next-generation sequencing (mNGS) has proven to be a valuable tool in detecting pathogens in patients with suspected CNS infection. By sequencing microbial nucleic acids present in a patient's cerebrospinal fluid, brain tissue, or samples collected outside of the CNS, such as plasma, mNGS can detect a wide range of pathogens, including rare, unexpected, and/or fastidious organisms. Furthermore, its target-agnostic approach allows for the identification of both known and novel pathogens. This is particularly useful in cases where conventional diagnostic methods fail to provide an answer. In addition, mNGS can detect multiple microorganisms simultaneously, which is crucial in cases of mixed infections without a clear predominant pathogen. Overall, clinical mNGS testing can help expedite the diagnostic process for CNS infections, guide appropriate management decisions, and ultimately improve clinical outcomes. However, there are key challenges surrounding its use that need to be considered to fully leverage its clinical impact. For example, only a few specialized laboratories offer clinical mNGS due to the complexity of both the laboratory methods and analysis pipelines. Clinicians interpreting mNGS results must be aware of both false negatives-as mNGS is a direct detection modality and requires a sufficient amount of microbial nucleic acid to be present in the sample tested-and false positives-as mNGS detects environmental microbes and their nucleic acids, despite best practices to minimize contamination. Additionally, current costs and turnaround times limit broader implementation of clinical mNGS. Finally, there is uncertainty regarding the best practices for clinical utilization of mNGS, and further work is needed to define the optimal patient population(s), syndrome(s), and time of testing to implement clinical mNGS.

Therapeutic drug monitoring of polymyxin B cerebrospinal fluid concentrations in patients with carbapenem-resistant Gram-negative bacteria-induced central nervous system infection.

OBJECTIVES: Central nervous system (CNS) infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) present a major health and economic burden worldwide. This multicentre prospective study aimed to assess the feasibility and usefulness of CSF therapeutic drug monitoring (TDM) after intrathecal/intraventricular administration of polymyxin B in patients with CNS infections. METHODS: Forty-two patients treated with intrathecal/intraventricular administration of polymyxin B against CR-GNB-induced CNS infections were enrolled. CSF trough level (Cmin) was collected beginning on Day 2 post-polymyxin B initiation and thereafter. The primary outcomes were clinical cure and 28-day all-cause mortality. RESULTS: All patients started with intrathecal/intraventricular administration of polymyxin B at a dose of 5 g/day, corresponding to a median CSF Cmin of 2.93 mg/L (range, 0.21-25.74 mg/L). Clinical cure was 71.4%, and the median CSF Cmin of this group was higher than that of clinical failure group [3.31 (IQR, 1.73-5.62) mg/L versus 2.25 (IQR, 1.09-4.12) mg/L; P = 0.011]. In addition, with MICs ≤ 0.5 mg/L, maintaining polymyxin B CSF Cmin above 2.0 mg/L showed a higher clinical cure rate (P = 0.041). The 28-day all-cause mortality rate was 31.0% and had no association with CSF Cmin. CONCLUSIONS: After intrathecal/intraventricular administration of polymyxin B, CSF concentrations fluctuated considerably inter- and intra-individual. Polymyxin B CSF Cmin above 2.0 mg/L was associated with clinical cure when MICs were ≤ 0.5 mg/L, and the feasibility of TDM warrants additional clinical studies.

Neuroinfectious Emergencies.

OBJECTIVE: This article describes nervous system infections and complications that lead to neurologic emergencies. LATEST DEVELOPMENTS: New research on the use of dexamethasone in viral and fungal infections is reviewed. The use of advanced MRI techniques to evaluate nervous system infections is discussed. ESSENTIAL POINTS: Neurologic infections become emergencies when they lead to a rapid decline in a patient's function. Emergent complications may result from neurologic infections that, if not identified promptly, can lead to permanent deficits or death. These complications include cerebral edema and herniation, spinal cord compression, hydrocephalus, vasculopathy resulting in ischemic stroke, venous thrombosis, intracerebral hemorrhage, status epilepticus, and neuromuscular respiratory weakness.

Contribution of CNS and extra-CNS infections to neurodegeneration: a narrative review.

Central nervous system infections have been suggested as a possible cause for neurodegenerative diseases, particularly sporadic cases. They trigger neuroinflammation which is considered integrally involved in neurodegenerative processes. In this review, we will look at data linking a variety of viral, bacterial, fungal, and protozoan infections to Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis and unspecified dementia. This narrative review aims to bring together a broad range of data currently supporting the involvement of central nervous system infections in the development of neurodegenerative diseases. The idea that no single pathogen or pathogen group is responsible for neurodegenerative diseases will be discussed. Instead, we suggest that a wide range of susceptibility factors may make individuals differentially vulnerable to different infectious pathogens and subsequent pathologies.

[Concerns of Performance Evaluation on Central Nervous System Infection Pathogen Metagenome Sequencing Reagent].

From the perspective of the performance evaluation, concerns of the range of pathogens, establishment of enterprise reference material, reaction system study and analytical performances evaluation of central nervous system infection pathogen metagenome sequencing reagent are briefly described, including study methods and quality control requirements. This study is intended to increase the research and development efficiency of products, and contribute to the development of associated industry.

Biomarkers and genotypes in patients with Central nervous system infection caused by enterovirus.

PURPOSE: Enteroviruses (EV) comprises many different types and are the most common cause of aseptic meningitis. How the virus affects the brain including potential differences between types are largely unknown. Measuring biomarkers in CSF is a tool to estimate brain damage caused by CNS infections. METHODS: A retrospective study was performed in samples from 38 patients with acute neurological manifestations and positive CSF-EV RNA (n = 37) or serum-IgM (n = 1). The EV in 17 samples were typed by sequencing. The biomarkers neurofilament light (NFL), glial fibrillary acidic protein (GFAP), S-100B protein, amyloid-ß (Aß) 40 and Aß42, total-tau (T-tau) and phosphorylated tau (P-tau) were measured and compared with data derived from a control group (n = 19). RESULTS: There were no increased levels of GFAP (p ≤ 0.1) nor NFL (p ≤ 0.1) in the CSF of patients with EV meningitis (n = 38) compared with controls. However, we found decreased levels of Aß42 (p < 0.001), Aß40 (p < 0.001), T-tau (p ≥ 0.01), P-tau (p ≤ 0.001) and S-100B (p ≤ 0.001). E30 (n = 9) and CVB5 (n = 6) were the most frequent EV-types identified, but no differences in biomarker levels or other clinical parameters were found between the infecting virus type. Seven patients who were followed for longer than one month reported remaining cognitive impairment, although no correlations with biomarker concentrations were observed. CONCLUSION: There are no indication of neuronal or astrocyte damage in patients with EV meningitis. Yet, decreased concentrations of Aß40, Aß42, P-tau and T-tau were shown, a finding of unknown importance. Cognitive impairment after acute disease occurs, but with only a limited number of patients analysed, no conclusion can be drawn concerning any association with biomarker levels or EV types.

Tenascin-C in patients with central nervous system infections.

BACKGROUND: The extracellular matrix protein tenascin-C has been discovered to be an important regulator of the response to tissue injury and repair in cerebrovascular diseases. This study investigated if tenascin-C is released in response to infections in the central nervous system (CNS). METHODS: Tenascin-C concentration in the cerebrospinal fluid (CSF) was measured in patients, (>18 years) with and without CNS infections, admitted to a department of infectious diseases in Denmark. CSF tenascin-C was measured on the Meso-scale platform. RESULTS: 174 patients were included of which 140 were diagnosed with a CNS infection and 34 where this was ruled out (control group). Median CSF tenascin-C levels were significantly higher among patients with bacterial meningitis (147 pg/mL), viral meningitis (33 mg/mL), viral encephalitis (39 pg/mL) and Lyme neuroborreliosis (45 pg/mL) when compared to controls (21 pg/mL). Correlations between tenascin-C and CSF markers of inflammation and age were only moderate. CONCLUSION: Levels of CSF tenascin-C are higher among patients with bacterial and viral neuroinfections, already on admission, but exhibit only a modest correlation with baseline indices of neuroinflammation. CSF tenascin-C is highest among patients with bacterial meningitis compared to the other CNS infections. Patients with unfavorable outcomes presented with higher median CSF tenascin-C than their counterparts.

Solid organ transplant-related central nervous system infections.

PURPOSE OF REVIEW: Central nervous system (CNS) infections in solid organ transplant (SOT) recipients may present atypical or nonspecific symptoms. Due to a wider range of infectious agents compared with immunocompetent hosts, diagnosis is challenging. This review categorizes CNS infections in SOT recipients by cause. RECENT FINDINGS: New studies have reported new data on the epidemiology and the risk factors associated with each specific pathogen described in this review. Additionally, we included the treatment recommendations. SUMMARY: The latest findings give us an insight into the different pathogens causing infectious neurologic complications in SOT recipients.

Metagenomic Next-Generation Sequencing Contributes to the Early Diagnosis of Mixed Infections in Central Nervous System.

Central nervous system (CNS) infections represent a challenge due to the complexities associated with their diagnosis and treatment, resulting in a high incidence rate and mortality. Here, we presented a case of CNS mixed infection involving Candida and human cytomegalovirus (HCMV), successfully diagnosed through macrogenomic next-generation sequencing (mNGS) in China. A comprehensive review and discussion of previously reported cases were also provided. Our study emphasizes the critical role of early pathogen identification facilitated by mNGS, underscoring its significance. Notably, the integration of mNGS with traditional methods significantly enhances the diagnostic accuracy of CNS infections. This integrated approach has the potential to provide valuable insights for clinical practice, facilitating early diagnosis, allowing for treatment adjustments, and ultimately, improving the prognosis for patients with CNS infections.

Temporal and spatial dynamics of Listeria monocytogenes central nervous system infection in mice.

Listeria monocytogenes is a bacterial pathogen that can cause life-threatening central nervous system (CNS) infections. While mechanisms by which L. monocytogenes and other pathogens traffic to the brain have been studied, a quantitative understanding of the underlying dynamics of colonization and replication within the brain is still lacking. In this study, we used barcoded L. monocytogenes to quantify the bottlenecks and dissemination patterns that lead to cerebral infection. Following intravenous (IV) inoculation, multiple independent invasion events seeded all parts of the CNS from the blood, however, only one clone usually became dominant in the brain. Sequential IV inoculations and intracranial inoculations suggested that clones that had a temporal advantage (i.e., seeded the CNS first), rather than a spatial advantage (i.e., invaded a particular brain region), were the main drivers of clonal dominance. In a foodborne model of cerebral infection with immunocompromised mice, rare invasion events instead led to a highly infected yet monoclonal CNS. This restrictive bottleneck likely arose from pathogen transit into the blood, rather than directly from the blood to the brain. Collectively, our findings provide a detailed quantitative understanding of the L. monocytogenes population dynamics that lead to CNS infection and a framework for studying the dynamics of other cerebral infections.

Characteristics and Risk Factors of Central Nervous System Infection in Children With Febrile Seizures.

OBJECTIVE: The aim of the present study is to evaluate the necessity of performing lumbar puncture in patients experiencing febrile seizures, considering the epidemiology specific to Brazil. METHODS: A retrospective cross-sectional study was performed from January 2017 to December 2021. RESULTS: A total of 469 children with seizure and fever were analyzed. The identified event was the first in 65.9% (n = 309). A total of 54.2% (n = 254) of patients had a simple febrile seizure. Infectious focus, excluding previous central nervous system (CNS) infection, was identified in 35.6% (n = 167) patients. Meningitis was identified in 7.7% (n = 36) patients, all of them were viral. Patients with CNS infection had a higher frequency of symptoms such as nausea and vomiting, drowsiness, headache, and higher level of leukocytosis. A longer duration of fever was found to be more strongly associated with CNS infection. CONCLUSIONS: When considering the use of lumbar puncture in febrile seizure, it is important to conduct a comprehensive evaluation that considers multiple factors, including clinical signs, symptoms, and the overall clinical context. Meningeal signs may be less prominent, and other symptoms such as lethargy, irritability, and vomiting may serve as more reliable indicators. Although clinical examination suggestive of meningitis remains an important factor, the recurrence of febrile seizures and a longer length of fever can provide additional insights and aid in decision-making regarding lumbar puncture.

Clinical course and peculiarities of Parechovirus and Enterovirus central nervous system infections in newborns: a single-center experience.

Parechovirus (HpEV) and Enterovirus (EV) infections in children mostly have a mild course but are particularly fearsome in newborns in whom they may cause aseptic meningitis, encephalitis, and myocarditis. Our study aimed to describe the clinical presentations and peculiarities of CNS infection by HpEV and EV in neonates. This is a single-center retrospective study at Istituto Gaslini, Genoa, Italy. Infants aged ≤ 30 days with a CSF RTq-PCR positive for EV or HpEV from January 1, 2022, to December 1, 2023, were enrolled. Each patient's record included demographic data, blood and CSF tests, brain MRI, therapies, length of stay, ICU admission, complications, and mortality. The two groups were compared to identify any differences and similarities. Twenty-five patients (15 EV and 10 HpEV) with a median age of 15 days were included. EV patients had a more frequent history of prematurity/neonatal respiratory distress syndrome (p = 0.021), more respiratory symptoms on admission (p = 0.012), and higher C-reactive protein (CRP) levels (p = 0.027), whereas ferritin values were significantly increased in HpEV patients (p = 0.001). Eight patients had a pathological brain MRI, equally distributed between the two groups. Three EV patients developed myocarditis and one HpEV necrotizing enterocolitis with HLH-like. No deaths occurred.  Conclusion: EV and HpEV CNS infections are not easily distinguishable by clinical features. In both cases, brain MRI abnormalities are not uncommon, and a severe course of the disease is possible. Hyper-ferritinemia may represent an additional diagnostic clue for HpEV infection, and its monitoring is recommended to intercept HLH early and initiate immunomodulatory treatment. Larger studies are needed to confirm our findings. What is Known: • Parechovirus and Enteroviruses are the most common viral pathogens responsible for sepsis and meningoencephalitis in neonates and young infants. • The clinical course and distinguishing features of Parechovirus and Enterovirus central nervous system infections are not well described. What is New: • Severe disease course, brain MRI abnormalities, and complications are not uncommon in newborns with Parechovirus and Enteroviruses central nervous system infections. • Hyper-ferritinemia may represent an additional diagnostic clue for Parechovirus infection and its monitoring is recommended.

Microbiomes detected by cerebrospinal fluid metagenomic next-generation sequencing among patients with and without HIV with suspected central nervous system infection.

BACKGROUND: Opportunistic infections in the central nervous system (CNS) can be a serious threat to people living with HIV. Early aetiological diagnosis and targeted treatment are crucial but difficult. Metagenomic next-generation sequencing (mNGS) has significant advantages over traditional detection methods. However, differences in the cerebrospinal fluid (CSF) microbiome profiles of patients living with and without HIV with suspected CNS infections using mNGS and conventional testing methods have not yet been adequately evaluated. METHODS: We conducted a retrospective cohort study in the first hospital of Changsha between January 2019 and June 2022 to investigate the microbiomes detected using mNGS of the CSF of patients living with and without HIV with suspected CNS infections. The pathogens causing CNS infections were concurrently identified using both mNGS and traditional detection methods. The spectrum of pathogens identified was compared between the two groups. RESULTS: Overall, 173 patients (140 with and 33 without HIV) with suspected CNS infection were enrolled in our study. In total, 106 (75.7%) patients with and 16 (48.5%) patients without HIV tested positive with mNGS (p = 0.002). Among the enrolled patients, 71 (50.7%) with HIV and five (15.2%) without HIV tested positive for two or more pathogens (p < 0.001). Patients with HIV had significantly higher proportions of fungus (20.7% vs. 3.0%, p = 0.016) and DNA virus (59.3% vs. 21.2%, p < 0.001) than those without HIV. Epstein-Barr virus (33.6%) was the most commonly identified potential pathogen in the CSF of patients living with HIV using mNGS, followed by cytomegalovirus (20.7%) and torque teno virus (13.8%). The top three causative pathogens identified in patients without HIV were Streptococcus (18.2%), Epstein-Barr virus (12.1%), and Mycobacterium tuberculosis (9.1%). In total, 113 patients living with HIV were diagnosed as having CNS infections. The rate of pathogen detection in people living with HIV with a CNS infection was significantly higher with mNGS than with conventional methods (93.8% vs. 15.0%, p < 0.001). CONCLUSION: CSF microbiome profiles differ between patients living with and without HIV with suspected CNS infection. mNGS is a powerful tool for the diagnosis of CNS infection among people living with HIV, especially in those with mixed infections.

Central nervous system infections in the tropics.

PURPOSE OF REVIEW: Emerging and re-emerging central nervous system (CNS) infections are a major public health concern in the tropics. The reasons for this are myriad; climate change, rainfall, deforestation, increased vector density combined with poverty, poor sanitation and hygiene. This review focuses on pathogens, which have emerged and re-emerged, with the potential for significant morbidity and mortality. RECENT FINDINGS: In recent years, multiple acute encephalitis outbreaks have been caused by Nipah virus, which carries a high case fatality. Arboviral infections, predominantly dengue, chikungunya and Zika are re-emerging increasingly especially in urban areas due to changing human habitats, vector behaviour and viral evolution. Scrub typhus, another vector borne disease caused by the bacterium Orientia tsutsugamushi , is being established as a leading cause of CNS infections in the tropics. SUMMARY: A syndromic and epidemiological approach to CNS infections in the tropics is essential to plan appropriate diagnostic tests and management. Rapid diagnostic tests facilitate early diagnosis and thus help prompt initiation and focusing of therapy to prevent adverse outcomes. Vector control, cautious urbanization and deforestation, and reducing disturbance of ecosystems can help prevent spread of vector-borne diseases. Regional diagnostic and treatment approaches and specific vaccines are required to avert morbidity and mortality.