This article reports a male patient，aged 31 years，who were admitted due to sudden-onset speech and language impairment and limb weakness at the right side for more than 7 hours and achieved successful revascularization after endovascular treatment. Etiological screening revealed positive treponema pallidum particle agglutination （1∶1 280） and positive HIV antibodies in serum，as well as an increase in white blood cell count and positive TPPA （1∶640） in cerebrospinal fluid （CSF）. High-resolution magnetic resonance imaging of the vessel wall showed inflammatory changes in the vessel wall of the M1 segment of the left middle cerebral artery. After multidisciplinary consultation，the patient was diagnosed with acute ischemic stroke secondary to cerebral arteritis caused by neurosyphilis and HIV infection and was given antiplatelet therapy，benzathine penicillin for syphilis，and antiviral therapy. After 6 months of follow-up，the patient had a modified Rankin Scale score of 0 and achieved clearance of syphilis-related indicators in serum and CSF，and CT angiography confirmed revascularization without new-onset stenosis. The literature review shows that acute ischemic stroke is a common manifestation of co-infection with HIV and neurosyphilis in young individuals，and early syphilis detection in serum and CSF，HIV screening，and timely combination therapy are of great significance for improving prognosis.
Neurosyphilis ; Arteritis

OBJECTIVES: To investigate the therapeutic effects of inulin-type oligosaccharides of Morinda officinalis (IOMO) in a murine model of Streptococcus pneumoniae meningitis (SPM) and explore its possible mechanisms. METHODS: A total of 120 male C57BL/6J mice were randomly assigned into Sham, SPM+Saline, SPM+IOMO (25 mg/kg), and SPM+IOMO (50 mg/kg) groups. After modeling, the mice received daily gavage of saline or IOMO at the indicated doses for 7 consecutive days, and the changes in symptom scores and mortality of the mice were monitored. Brain pathology and neuronal injury of the mice were assessed using HE and Nissl staining, and qRT-PCR was performed to detect mRNA levels of the inflammatory mediators. Brain edema and blood-brain barrier (BBB) permeability of the mice were evaluated by measuring brain water content and Evans blue (EB) staining; Western blotting was used to analyze the expressions of BBB-associated proteins, and flow cytometry was employed to detect IFN‑γ expression level in the infiltrating lymphocytes. Open-field test (OFT) and novel object recognition test (NORT) were conducted to assess learning and memory ability of the mice on day 21 after modeling. RESULTS: IOMO treatment at 50 mg/kg significantly reduced the symptom scores and mortality rate of SPM mice, alleviated brain damage, and downregulated mRNA levels of IL-6, TNF‑α, IL-1β, IL-18, IFN‑γ, iNOS, NLRP3, ASC, caspase-1 and GSDMD in the brain tissue. IOMO treatment also decreased brain water content and EB leakage, upregulated VE-cadherin and occludin expressions, and suppressed AQP4, iNOS, and IFN‑γ levels of the mice. IOMO-treated mice exhibited improved learning and memory compared with the saline-treated mice on day 21 after SPM modeling. CONCLUSIONS IOMO alleviates SPM symptoms, reduces mortality, and mitigates cognitive deficits in mice possibly by suppressing cerebral inflammation and protecting BBB functions.
Animals ; Morinda/chemistry* ; Mice, Inbred C57BL ; Male ; Mice ; Meningitis, Pneumococcal/drug therapy* ; Blood-Brain Barrier/metabolism* ; Inulin/therapeutic use* ; Oligosaccharides/therapeutic use* ; Disease Models, Animal ; Interferon-gamma/metabolism* ; Brain Edema

Neurosyphilis （NS） is a group of diseases with a series of nervous system symptoms when Treponema pallidum infects the central nervous system， with an unknown pathogenesis and significant heterogeneity in clinical manifestations. It is called the “universal imitator”， leading to a high misdiagnosis rate in clinical practice. Cognitive impairment is one of the most common clinical manifestations of NS， but delayed diagnosis may cause irreversible neuronal damage. Therefore， early identification of NS with the main manifestation of mild cognitive impairment is of great importance for achieving a good prognosis of patients. This article reports a case of NS with the main manifestation of mild cognitive impairment and reviews its clinical features， in order to improve the understanding of this disease among clinicians.
Neurosyphilis

Neurosyphilis (NS) is an infectious disease caused by Treponema pallidum invading the central nervous system. It can manifest at any stage of syphilis, and is often misdiagnosed due to its atypical and progressive symptoms. The increasing incidence of NS underscores the necessity for early and accurate diagnosis. Here, we present a case where routine cerebrospinal fluid metagenomic next-generation sequencing (mNGS) was used to diagnose a patient with neurosyphilis. The patient exhibited cognitive impairment and was initially diagnosed with cerebral infarction due to syphilitic cerebral arteritis. Thus, the patient was treated with dual antiplatelet therapy (aspirin and clopidogrel) and statins to stabilize the plaques. Neurosyphilis was treated with penicillin sodium injections, resulting in significant improvement in the patient's mental state. This case is a rare instance of neurosyphilis associated with cerebral infarction. These findings suggest that mNGS is a valuable tool in diagnosing neurosyphilis, potentially improving diagnostic accuracy and patient outcomes.
Humans ; Anti-Bacterial Agents/therapeutic use* ; Cognitive Dysfunction/etiology* ; High-Throughput Nucleotide Sequencing ; Neurosyphilis/drug therapy* ; Treponema pallidum/isolation & purification*

Objective: To investigate the prevalence and poor prognosis of late-onset sepsis (LOS) in very low birth weight infant (VLBWI). Methods: This prospective, multicenter observational cohort study was conducted based on the data from Sina-Northern Neonatal Network (SNN). The general data, perinatal information and poor prognosis of 6 639 VLBWI, who were admitted to the 35 neonatal intensive care units from 2018 to 2021, were collected and analyzed. According to the occurrence of LOS during hospitalization, the VLBWI were assigned to the LOS group and non-LOS group. The LOS group was further divided into 3 subgroups according to the occurrence of neonatal necrotizing enterocolitis (NEC) and purulent meningitis. The Chi-square test or Fisher exact probability method, independent sample t test, Mann-Whitney U test and multivariate Logistic regression model were used to analyze the relationship between LOS and poor prognosis in VLBWI. Results: A total of 6 639 eligible VLBWI were enrolled, including 3 402 cases (51.2%) of males and 1 511 cases (22.8%) with LOS. The incidences of LOS in extremely low birth weight infants (ELBWI) and extremely preterm infants were 33.3% (392/1 176) and 34.2% (378/1 105), respectively. There were 157 cases (10.4%) who died in the LOS group and 48 cases (24.9%) in the subgroup of LOS complicated with NEC. Multivariate Logistic regression analysis showed that LOS complicated with NEC was associated with increased mortality and incidence of grade Ⅲ-Ⅳ intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL), moderate or severe bronchopulmonary dysplasia (BPD), and extrauterin growth retardation (EUGR) (OR_adjust=5.27, 2.59, 3.04, 2.04; 95%CI 3.60-7.73, 1.49-4.50, 2.11-4.37, 1.50-2.79; all P<0.01); LOS complicated with purulent meningitis was also associated with increased mortality and incidence of grade Ⅲ-Ⅳ IVH or PVL, and moderate or severe BPD (OR_adjust=2.22, 8.13, 3.69, 95%CI 1.30-3.37, 5.22-12.67, 2.49-5.48; all P<0.01); the infants without NEC or purulent meningitis in the LOS group was only associated with increased incidence of moderate or severe BPD (OR_adjust=2.20, 95%CI 1.83-2.65, P<0.001). After ruling out contaminated bacteria, a total of 456 cases showed positive blood culture, including 265 cases (58.1%) of Gram-negative bacteria, 126 cases (27.6%) of Gram-positive bacteria, and 65 cases (14.3%) of fungi. The most common pathogenic bacteria was Klebsiella pneumoniae (n=147, 32.2%), followed by coagulase-negative Staphylococcus (n=72, 15.8%) and subsequently Escherichia coli (n=39, 8.6%). Conclusions: The incidence of LOS is high in VLBWI. Klebsiella pneumoniae is the most common pathogenic bacteria, followed by coagulase-negative Staphylococcus and Escherichia coli. LOS is associated with a poor prognosis for moderate to severe BPD. The prognosis of LOS complicated with NEC is poor with the highest mortality, and the risk of brain damage is significantly increased when LOS complicated with purulent meningitis.
Infant ; Male ; Female ; Pregnancy ; Infant, Newborn ; Humans ; Prospective Studies ; Coagulase ; Infant, Extremely Low Birth Weight ; Sepsis/epidemiology* ; Bronchopulmonary Dysplasia ; Escherichia coli ; Infant, Extremely Premature ; Meningitis

Objective: To explore the value of metagenomic next-generation sequencing (mNGS) in the etiology diagnosis of bacterial meningitis in children. Methods: The etiological results of 189 children diagnosed with "bacterial meningitis" or "purulent meningitis" or "central nervous system infection" in the Children's Hospital of Fudan University from 1st January 2019 to 31st December 2020 were analyzed retrospectively. The cerebrospinal fluid (CFS) of the children with bacterial meningitis was detected by culture and mNGS respectively, and the difference of pathogen detection rate between the 2 methods was analyzed. According to the age at the time of visit, the children were divided into neonatal group (≤28 days of age) and non-neonatal group (>28 days of age), and χ² test was used to compare the positive rate between the 2 groups. Taking CFS culture as the gold standard, the sensitivity and specificity of mNGS in the diagnosing of bacterial meningitis in children were analyzed. Results: Among these 189 children with bacterial meningitis, 116 were males and 73 were females. A total of 76 strains of pathogens were detected in blood and (or) CSF cultures, of which 50 strains (65.8%) were Gram-positive bacteria; among those, 18 strains (23.7%) of Streptococcus agalactiae, 17 strains (19.7%) of Escherichia coli and 15 strains (19.7%) of Streptococcus pneumoniae were detected with higher detection rate. The infection rate of Gram-positive bacteria in the non-neonatal group was higher than that in the neonatal group (76.0% (38/50) vs. 50.0% (13/26), χ²=5.24, P=0.020).The same CSF samples of 48 cases were tested by mNGS and culture at the same time, and the detection rate of mNGS was higher than that of CSF culture (20 cases (41.7%) vs. 12 cases (25.0%), χ²=16.45, P<0.001). The consistency of mNGS and culture results was 79.2% (38/48), and the same pathogen was detected in 11 children with both positive mNGS and CSF culture. Taking the results of CSF culture as the gold standard, the sensitivity of mNGS in the diagnosing of bacterial meningitis was 91.7%, and the specificity was 75.0%. Conclusions: The mNGS technology can improve the pathogen detection rate of bacterial meningitis in children, and has a high consistency with CSF culture. In suspected cases where the pathogen cannot be identified by traditional methods, CSF mNGS should be considered timely.
Child ; Escherichia coli ; Fatigue Syndrome, Chronic ; Female ; Gram-Positive Bacteria ; High-Throughput Nucleotide Sequencing/methods* ; Humans ; Male ; Meningitis, Bacterial/microbiology* ; Metagenomics/methods* ; Retrospective Studies ; Sensitivity and Specificity

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Epidemic cerebrospinal meningitis (meningococcal meningitis) is an acute respiratory infectious disease with high mortality and serious sequelae. Meningococcal vaccine is an effective measure to prevent and control meningococcal meningitis. At present, group B meningococcal meningitis has become the main prevalent serum group in the world, including China. Meningococcal ACYW and other vaccines are mainly composed of capsular polysaccharides, while the main component of group B meningococcal vaccine is protein, including outer membrane vesicles (OMV) and recombinant protein vaccine. The methods for evaluating the immunogenicity of group B meningococcal vaccine include hSBA and alternative methods such as meningococcal antigen typing system (MATS), flow cytometric meningococcal antigen surface expression assay (MEASURE), genetic meningococcal antigen typing system (gMATS) and bexsero antigen sequence type (BAST). The evaluation of vaccine immunogenicity is the basis of vaccine development and clinical trial research, However, at present, there is no group B meningococcal vaccine in China. Therefore, in this paper, the research progress of immunogenicity evaluation of group B meningococcal vaccine has been reviewed, in order to provide technical guidance for the research and development of group B meningococcal vaccine, immunogenicity evaluation and clinical trial research in China.
Humans ; Meningitis, Meningococcal/prevention & control* ; Meningococcal Vaccines ; Neisseria meningitidis ; Serogroup ; Vaccines, Combined

Two cases of epidemic situation of serogroup B meningitis in infants in Shandong Province in 2021 were investigated. Samples of cases and their close contacts were collected for isolation, culture and identification of Neisseria meningitides (Nm). The isolates were subjected to multi-locus sequence typing, outer membrane protein porA and fetA genotyping and drug sensitivity test. Two laboratory-confirmed outbreaks of serogroup B meningitis were reported from Yantai city and Linyi city. The indicated cases were infants aged 5 months and 2 months old respectively. They were not vaccinated with meningitis vaccine. Their epidemiological characteristics and clinical manifestations were similar and the prognosis was good. The same sequence type (ST) of serogroup B Nm strains as the indicated cases was detected in the samples of close family contacts, but without subsequent cases. Among them, Yantai strain was were identified as the type ST-8920, belonging to CC4821 clonal complex, and the genotypes of porA and fetA were p1.21-2, 23 and F3-1. Linyi strain was a new type, belonging to CC4821 clonal complex and the genotypes of porA and fetA were p1.20, 23 and F1-91. The above strains were resistant to penicillin, ciprofloxacin, levofloxacin and Chemitrim, and their sensitivity to cephalosporin decreased. Two cases of infant serogroup B epidemic were relatively rare in China, which were different from the epidemiological and pathogenic characteristics of other Nm serogroups in the past.
Epidemics ; Humans ; Infant ; Meningitis, Meningococcal/epidemiology* ; Multilocus Sequence Typing ; Neisseria meningitidis ; Serogroup

Objective: To investigate the relationship between nutritional risk status and clinical outcome in children with tuberculous meningitis (TBM). Methods: The clinical data (basic information, clinical symptoms and laboratory test results) of 112 patients with TBM, who were admitted to Department of Pediatric Infectious Diseases of West China Second Hospital of Sichuan University,from January 2013 to December 2020 were retrospectively analyzed. The patients were divided into the nutritional risk group and the non-nutritional risk group according to the assessment of the nutritional risk by the STRONGkids Scale. The variables of basic information, clinical symptoms and laboratory test measurements etc. were compared between the two groups by using Student t test, Rank sum test or Chi-square test. Multivariate Logistic regression analysis were used to analyze nutritional risk factors. Results: Among 112 patient with TBM, 55 were males and 57 females. There were 62 cases in the nutritional risk group and 50 cases in the non-nutritional risk group. The proportion of cases with nutritional risk was 55.4% (62/112). Patients in the nutritional risk who lived in rural areas, had symptoms of brain nerve damage, convulsions, emaciation and anorexia, with a diagnosis time of ≥21 days, and the level of cerebrospinal fluid (CSF) protein were all higher than those in the non-nutritional risk group ((50 cases (80.6%) vs. 32 cases (64.0%), 20 cases (32.3%) vs.8 cases (16.0%), 33 cases (53.2%) vs. 15 cases (30.0%), 30 cases (48.4%) vs. 2 cases (4.0%), 59 cases (95.2%) vs. 1 case (2.0%),41 cases (66.1%) vs.18 cases (36.0%), 1 406 (1 079, 2 068) vs. 929 (683, 1 208) mg/L, χ²=3.91, 3.90, 6.10, 26.72, 98.58, 10.08, Z=4.35, all P<0.05). The levels of serum albumin,hemoglobin,lymphocyte count, white blood cell count, and CSF glucose were significantly lower in patients with nutritional risk ((36±5) vs. (41±4) g/L, (110±17) vs. (122±14) g/L, 1.4 (1.0, 2.0)vs. 2.3 (1.6, 3.8)×10⁹/L, 7.8 (6.3, 10.0)×10⁹ vs. 10.0 (8.3, 12.8)×10⁹/L, 1.0 (0.8, 1.6) vs. 2.1 (1.3, 2.5) mmol/L, t=-6.15, -4.22, Z=-4.86, -3.92, -4.16, all P<0.05).Increased levels of serum albumin (OR=0.812, 95%CI:0.705-0.935, P=0.004) and lymphocyte count (OR=0.609, 95%CI:0.383-0.970, P=0.037) may reduce the nutritional risk of children with TBM; while convulsions (OR=3.853, 95%CI:1.116-13.308, P=0.033) and increased level of CSF protein (OR=1.001,95%CI:1.000-1.002, P=0.015) may increase the nutritional risk of children with TBM. Similarly, the rate of complications and drug-induced liver injury was higher in the nutritional risk group (47 cases (75.8%) vs. 15 cases(30.0%), 31 cases (50.0%) vs.8 cases (16.0%), χ²=23.50, 14.10, all P<0.05). Moreover, the length of hospital stay was also longer in the nutritional risk group ((27±13) vs. (18±7) d, t=4.38, P<0.05). Conclusions: Children with TBM have a high incidence of nutritional risk. Convulsive, the level of serum albumin, the level of lymphocyte count and CSF protein may affect the nutritional risk of children with TBM. The nutritional risk group has a high incidence of complications and heavy economic burden.It is necessary to carry out nutritional screening and nutritional support for children with TBM as early as possible.
Female ; Humans ; Leukocyte Count ; Male ; Nutrition Assessment ; Nutritional Status ; Retrospective Studies ; Tuberculosis, Meningeal/diagnosis*