Burden and bacterial etiology of neonatal meningitis at Hawassa University Comprehensive Specialized Hospital, Hawassa, Ethiopia.

BACKGROUND: Meningitis poses a significant challenge to public health in low-income nations, such as Ethiopia, with a particular impact on newborns. The magnitude and etiologies of meningitis vary based on geographic location and age of patients. There is limited data regarding the magnitude and etiology of meningitis from Sidama Regional State, Ethiopia. This study aimed to determine the magnitude and bacterial profile of meningitis among newborns aged less than 90 days at Hawassa University Comprehensive Specialized Hospital (HUCSH). METHODS: A retrospective cross-sectional study was conducted among newborns under 90 days who were suspected of meningitis at HUCSH from January 2019 to July 2023, and for whom Cerebrospinal fluid (CSF) culture was performed. At HUCSH, bacteria are isolated and identified using standard microbiological techniques. Socio-demographic characteristics and culture results were extracted from the laboratory register. Data were entered into Excel and exported it to SPSS version 20 for analysis. RESULTS: Overall 1061 newborns suspected of meningitis were included in the study. Among the participants, 767 individuals (72.3%) fell within the age range of 8 to 90 days. Of the total participants, 437 (41.2%) were females. The magnitude of culture-confirmed meningitis was 90(8.5%) 95% CI: 6.8%-10.1%. The magnitude of culture-confirmed meningitis among newborns aged 0-7 days and 8-90 days were 1.6% and 6.9% respectively. The proportion of bacteria among newborns aged 0-7 days and 8-90 days were 18.9% and 81.1% respectively. Coagulase-negative Staphylococci (CONS) were the most common bacteria (n = 26; 28.9%) recovered followed by Acinetobacter species (n = 12, 13.3%), Escherichia coli (n = 9; 10%), and Klebsiella pneumoniae (n = 7; 7.8%). K. pneumoniae was the predominant bacteria among newborns within the age group of 0 to 7 days while Acinetobacter species was the most common among newborns within the 8 to 90 days age group. The prevalence of culture-confirmed neonatal meningitis was found to be greater in male newborns (x2 = 1.74, p = 0.18), newborns aged between 8 to 90 days (x2 = 0.07, p = 3.4), and newborns admitted in 2022 (x2 = 2.4, p = 0.66). CONCLUSIONS: In this study, the overall magnitude of culture-confirmed meningitis was relatively high. Culture-confirmed meningitis was high in newborns within the age range of 8 to 90 days. The most common bacteria were CONS in both age groups followed by Acinetobacter species, E. coli, and K. pneumoniae.

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.

Simultaneous Presentation of B-Acute Lymphoblastic Leukemia and Streptococcus agalactiae Meningitis in a 3-Year-old Girl.

Infection is a major cause of treatment-related morbidity and mortality in pediatric acute lymphoblastic leukemia (ALL). Most children with ALL who develop life-threatening bacterial infections do so during induction therapy. We describe a rare case of ALL presenting simultaneously with Streptococcus agalactiae group B Streptococcus bacteremia and meningitis in a 3-year-old girl. She received appropriate antimicrobial therapy and a 2-drug early induction regimen consisting of vincristine and dexamethasone, leading to slow neurologic recovery and a favorable initial response to anti-neoplastic therapy as evidenced by minimal residual disease of 1.12% on day 15 of induction.

Insight into the role of Streptococcus suis zinc metalloprotease C from the new serotype causing meningitis in piglets.

Streptococcus suis (S. suis) is an important gram-positive pathogen and an emerging zoonotic pathogen that causes meningitis in swine and humans. Although several virulence factors have been characterized in S. suis, the underlying mechanisms of pathogenesis are not fully understood. In this study, we identified Zinc metalloproteinase C (ZmpC) probably as a critical virulence factor widely distributed in S. suis strains. ZmpC was identified as a critical facilitator in the development of bacterial meningitis, as evidenced by the detection of increased expression of TNF-α, IL-8, and matrix metalloprotease 9 (MMP-9). Subcellular localization analysis further revealed that ZmpC was localized to the cell wall surface and gelatin zymography analysis showed that ZmpC could cleave human MMP-9. Mice challenge demonstrated that ZmpC provided protection against S. suis CZ130302 (serotype Chz) and ZY05719 (serotype 2) infection. In conclusion, these results reveal that ZmpC plays an important role in promoting CZ130302 to cause mouse meningitis and may be a potential candidate for a S. suis CZ130302 vaccine.

[A case of recurrent Campylobacter fetus meningitis, occurring two months after the |initial infection was successfully treated].

A 43-year-old man was admitted to our department due to fever and headache. The cerebrospinal fluid analysis confirmed bacterial meningitis. Campylobacter species were isolated from blood cultures on the third day of admission. The patient was treated with meropenem (MEPM) and discharged on the 17th day. However, he experienced a recurrence of meningitis and was readmitted on the 68th day, initiating MEPM therapy. Campylobacter fetus was isolated from cerebrospinal fluid cultures on the 74th day. MEPM was continued until the 81st day, followed by one month of minocycline (MINO) therapy. The patient had an uneventful recovery without further recurrence. This case highlights the potential for recurrence of Campylobacter fetus meningitis approximately two months after the resolution of the initial infection. In addition to carbapenem therapy for at least two weeks, the adjunctive administration of MINO may be beneficial.

A rare case report of meningoencephalitis caused by Streptococcus porcinus.

Acute pyogenic meningitis is a medical emergency. Bacteria are the major causative agents of pyogenic meningitis with Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis being the most common. Here, we describe a case of bacterial meningoencephalitis caused by Streptococcus porcinus. To our knowledge this is the first case described in literature. The patient was treated with ceftriaxone and supportive treatment.

Group A Streptococcal meningitis in children: a short case series and systematic review.

BACKGROUND: Group A streptococcal(GAS) meningitis is a severe disease with a high case fatality rate. In the era of increasing GAS meningitis, our understanding about this disease is limited. PURPOSE: To gain a better understanding about GAS meningitis. METHODS: Five new cases with GAS meningitis were reported. GAS meningitis related literatures were searched for systematic review in PUBMED and EMBASE. Case reports and case series on paediatric cases were included. Information on demographics, risk factors, symptoms, treatments, outcomes, and emm types of GAS was summarized. RESULTS: Totally 263 cases were included. Among 100 individuals, 9.9% (8/81) had prior varicella, 11.1% (9/81) had anatomical factors, and 53.2% (42/79) had extracranial infections. Soft tissue infections were common among infants (10/29, 34.5%), while ear/sinus infections were more prevalent in children ≥ 3 years (21/42, 50.0%). The overall case fatality rate (CFR) was 16.2% (12/74). High risk of death was found in patients with shock or systemic complications, young children(< 3 years) and cases related to hematogenic spread. The predominate cause of death was shock(6/8). Among the 163 patients included in case series studies, ear/sinus infections ranged from 21.4 to 62.5%, while STSS/shock ranged from 12.5 to 35.7%, and the CFR ranged from 5.9 to 42.9%. CONCLUSIONS: A history of varicella, soft tissue infections, parameningeal infections and CSF leaks are important clinical clues to GAS in children with meningitis. Young children and hematogenic spread related cases need to be closely monitored for shock due to the high risk of death.

A case of scrub typhus with meningitis as the onset: Case report and literature review.

RATIONALE: Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system infections are uncommon. PATIENT CONCERNS: A 17-year-old male presented with a 5-day history of fever and headaches. The MRI of the head revealed thickness and enhancement of the left temporal lobe and tentorium cerebelli, indicating potential inflammation. DIAGNOSES: The patient was diagnosed with a central nervous system infection. INTERVENTIONS: Ceftriaxone and acyclovir were administered intravenously to treat the infection, reduce fever, restore acid-base balance, and manage electrolyte disorders. OUTCOMES: Despite receiving ceftriaxone and acyclovir as infection therapy, there was no improvement. Additional multipathogen metagenomic testing indicated the presence of O tsutsugamushi infection, and an eschar was identified in the left axilla. The diagnosis was changed to scrub typhus with meningitis and the therapy was modified to intravenous doxycycline. Following a 2-day therapy, the body temperature normalized, and the fever subsided. CONCLUSIONS: The patient was diagnosed with scrub typhus accompanied by meningitis, and doxycycline treatment was effective. LESSION: Rarely reported cases of scrub typhus with meningitis and the lack of identifiable symptoms increase the chance of misdiagnosis or oversight. Patients with central nervous system infections presenting with fever and headache unresponsive to conventional antibacterial and antiviral treatment should be considered for scrub typhus with meningitis. Prompt multipathogen metagenomic testing is recommended to confirm the diagnosis and modify the treatment accordingly.

Integrating DNA/RNA microbe detection and host response for accurate diagnosis, treatment and prognosis of childhood infectious meningitis and encephalitis.

BACKGROUND: Infectious meningitis/encephalitis (IM) is a severe neurological disease that can be caused by bacterial, viral, and fungal pathogens. IM suffers high morbidity, mortality, and sequelae in childhood. Metagenomic next-generation sequencing (mNGS) can potentially improve IM outcomes by sequencing both pathogen and host responses and increasing the diagnosis accuracy. METHODS: Here we developed an optimized mNGS pipeline named comprehensive mNGS (c-mNGS) to monitor DNA/RNA pathogens and host responses simultaneously and applied it to 142 cerebrospinal fluid samples. According to retrospective diagnosis, these samples were classified into three categories: confirmed infectious meningitis/encephalitis (CIM), suspected infectious meningitis/encephalitis (SIM), and noninfectious controls (CTRL). RESULTS: Our pipeline outperformed conventional methods and identified RNA viruses such as Echovirus E30 and etiologic pathogens such as HHV-7, which would not be clinically identified via conventional methods. Based on the results of the c-mNGS pipeline, we successfully detected antibiotic resistance genes related to common antibiotics for treating Escherichia coli, Acinetobacter baumannii, and Group B Streptococcus. Further, we identified differentially expressed genes in hosts of bacterial meningitis (BM) and viral meningitis/encephalitis (VM). We used these genes to build a machine-learning model to pinpoint sample contaminations. Similarly, we also built a model to predict poor prognosis in BM. CONCLUSIONS: This study developed an mNGS-based pipeline for IM which measures both DNA/RNA pathogens and host gene expression in a single assay. The pipeline allows detecting more viruses, predicting antibiotic resistance, pinpointing contaminations, and evaluating prognosis. Given the comparable cost to conventional mNGS, our pipeline can become a routine test for IM.

Confronting multidrug-resistant Klebsiella meningitis after mid-clival Cerebrospinal Fluid leak repair: a therapeutic odyssey.

A man in his 40s with type 2 diabetes mellitus had persistent right-sided watery nasal discharge for 6 months following cerebrospinal fluid (CSF) leak repair at another hospital, prompting his visit to us due to recurring symptoms. Imaging revealed a CSF leak from the mid-clivus for which revision endoscopic CSF leak repair was done. Regrettably, he developed postoperative meningitis caused by multidrug-resistant (MDR) Klebsiella pneumoniaeManaging this complex case was a challenging task due to the pathogen's resistance to conventional drugs and the scarcity of scientific evidence. We initiated a culture-guided combination regimen with ceftazidime, avibactam, aztreonam and tigecycline. This decision stemmed from meticulous literature review and observed antibiotic synergy while testing for this organism.After 4 weeks of vigilant treatment, the patient's symptoms improved significantly, and CSF cultures were sterile. We present our approach to effectively confront and manage a challenging instance of postoperative MDR bacterial meningitis.

Group B Streptococcus transcriptome when interacting with brain endothelial cells.

Bacterial meningitis is a life-threatening infection of the central nervous system (CNS) that occurs when bacteria are able to cross the blood-brain barrier (BBB) or the meningeal-cerebrospinal fluid barrier (mBCSFB). The BBB and mBCSFB comprise highly specialized brain endothelial cells (BECs) that typically restrict pathogen entry. Group B Streptococcus (GBS or Streptococcus agalactiae) is the leading cause of neonatal meningitis. Until recently, identification of GBS virulence factors has relied on genetic screening approaches. Instead, we here conducted RNA-seq analysis on GBS when interacting with induced pluripotent stem cell-derived BECs (iBECs) to pinpoint virulence-associated genes. Of the 2,068 annotated protein-coding genes of GBS, 430 transcripts displayed significant changes in expression after interacting with BECs. Notably, we found that the majority of differentially expressed GBS transcripts were downregulated (360 genes) during infection of iBECs. Interestingly, codY, encoding a pleiotropic transcriptional repressor in low-G + C Gram-positive bacteria, was identified as being highly downregulated. We conducted qPCR to confirm the codY downregulation observed via RNA-seq during the GBS-iBEC interaction and obtained codY mutants in three different GBS background parental strains. As anticipated from the RNA-seq results, the [Formula: see text]codY strains were more adherent and invasive in two in vitro BEC models. Together, this demonstrates the utility of RNA-seq during the BEC interaction to identify GBS virulence modulators. IMPORTANCE: Group B Streptococcus (GBS) meningitis remains the leading cause of neonatal meningitis. Research work has identified surface factors and two-component systems that contribute to GBS disruption of the blood-brain barrier (BBB). These discoveries often relied on genetic screening approaches. Here, we provide transcriptomic data describing how GBS changes its transcriptome when interacting with brain endothelial cells. Additionally, we have phenotypically validated these data by obtaining mutants of a select regulator that is highly down-regulated during infection and testing on our BBB model. This work provides the research field with a validated data set that can provide an insight into potential pathways that GBS requires to interact with the BBB and open the door to new discoveries.

Neonatal sepsis with meningitis, ventriculitis and brain abscess caused by Edwardsiella tarda.

A case of neonatal sepsis caused by Edwardsiella tarda, an uncommon pathogen typically associated with aquatic lifeforms, is described. The infant presented in septic shock with seizures and respiratory failure and was found to have meningitis, ventriculitis and a brain abscess requiring drainage. Only a small number of case reports of neonatal E. tarda infection, several with sepsis with poor auditory or neurodevelopmental outcomes or meningitis, have been described in the literature. This case report suggests that E. tarda, while uncommon, can be a cause of serious central nervous system disease in the neonatal population and that an aggressive approach to pursuing and treating complications may lead to improved neurodevelopmental outcomes.

A novel biosensing strategy for identification of three important bacteria causing meningitis.

Bacterial meningitis is an acute infection which requires rapid diagnosis and treatment due to the high mortality and serious consequences of the disease. The purpose of this study was to design a homemade multiplex PCR and a novel fluorescence biosensor on chip (FBC) to detect three important agents of meningitis including Streptococcus pneumoniae (S. pneumoniae), Neisseria meningitidis (N. meningitidis), and Haemophilus influenzae (H. influenzae). The homemade multiplex PCR can diagnose three bacterial species simultaneously. Fabrication of FBC was carried out based on the deposition of lead nanoparticles on a quartz slide using the thermal evaporation method. Then, the SH-Cap Probe/Target ssDNA /FAM-Rep probe was loaded on lead film. The evaluation of the fluorescence reaction when the probes bind to the target ssDNA was assessed by a Cytation 5 Cell Imaging Multimode Reader Bio-Tek. The limit of detections (LOD) in homemade PCR and FBC to identify S. pneumoniae were 119 × 102 CFU/mL (0.27 ng/µL) and 380 CFU/mL (9 pg/µL), respectively. The LODs of homemade PCR and FBC for detection of N. meningitidis were 4.49 CFU/mL (1.1 pg/µL) and 13 × 103 CFU/mL (30 pg/µL), respectively. Our results confirmed the LODs of homemade PCR and FBC in detection of H. influenzae were 15.1 CFU/mL (30 fg/µL) and 41 × 102 CFU/mL (90 pg/ µL), respectively. Both techniques had appropriate sensitivity and specificity in detection of S. pneumoniae, N. meningitidis and H. influenzae.

Epidemiological and bacterial profile of childhood meningitis in Tunisia.

The worldwide burden of disease of bacterial meningitis remains high, despite the decreasing incidence following introduction of routine vaccination campaigns.The aim of our study was to evaluate the epidemiological and bacteriological profile of paediatric bacterial meningitis (BM) in Tunisian children, during the period 2003-2019, following the implementation of Haemophilus influenzae type b (Hib) vaccine (April 2011) and before 10-valent pneumoccocal conjugate vaccine (PCV10) introduction to the childhood immunization program.All bacteriologically confirmed cases of BM admitted to children's hospital of Tunis were recorded (January 2003 to April 2019). Serogroups of Neisseria meningitidis (Nm) and serotypes of Streptococcus pneumoniae (Sp) and H. influenzae (Hi) and antibiotic resistance were determined using conventional and molecular methods.Among 388 cases, the most frequent species were Sp (51.3%), followed by Nm (27.5%) and Hi (16.8%). We observed a significant decrease in Hi BM rate during the conjugated Hib vaccine use period (P < 0.0001). The main pneumococcal serotypes were 14, 19F, 6B, 23F and 19A and the serotype coverage of PCV10, PCV13, PCV15 and PCV20 was 71.3 and 78.8%, 79.4 and 81.9% respectively. The most frequent Nm serogroup was B (83.1%). Most Hi strains were of serotype b (86.9%). High levels of resistance were found: Sp and Nm to penicillin (respectively 60.1 and 80%) and Hi to ampicillin (42.6%). All meningococcal and Hi isolates were susceptible to third-generation cephalosporins and 7.2% of pneumococcal strains had decreased susceptibility to these antibiotics.The Hib conjugate vaccine decreased the rate of BM. Sp dominated the aetiology of BM in children in Tunisia. Conjugate vaccines introducing decreases not only BM cases but also antimicrobial resistance.

Epidemiology and antimicrobial resistance patterns of bacterial meningitis among hospitalized patients at a tertiary care hospital in Saudi Arabia: a six-year retrospective study.

INTRODUCTION: Bacterial meningitis poses significant medical challenges due to its acute inflammatory nature and potential for severe neurological complications, emphasizing the need for prompt diagnosis and treatment. Limited data exists on its epidemiology and antimicrobial resistance trends among hospitalized patients in Saudi Arabia. This study aimed to investigate these factors at a tertiary care hospital over six years. METHODS: A retrospective analysis was conducted on cerebrospinal fluid samples results from 222 bacterial meningitis cases among hospitalized patients between 2018 and 2023. Demographic, clinical, microbiological data, and antibiotic susceptibility patterns were collected and analyzed. RESULTS: Pseudomonas aeruginosa (43%) was the predominant pathogen isolated. Neonates (16%) and children (47%) were most affected population. Nosocomial meningitis accounted for 92% of cases, mainly in the intensive care settings (50.45%). Extended-spectrum beta-lactamase was the leading resistance pattern (12.2%). Seasonal variation was observed, with a peak incidence in October-November. CONCLUSION: The study highlights the substantial burden of bacterial meningitis among hospitalized patients, especially among high-risk groups. Emerging antimicrobial resistance emphasizes the need for optimized surveillance and stewardship. Future prospective research employing molecular techniques across multiple centers in the country is warranted to enhance understanding and guide public health strategies in Saudi Arabia.