RARE DISEASE
Meningococcal meningitis
Meningococcal meningitis
Meningococcal meningitis
Drug discovery
2
drugs
With orphan designations
Overview
Meningococcal meningitis, caused by Neisseria meningitidis, is a life-threatening bacterial infection of the meninges characterized by sudden fever, neck stiffness, altered mental status, and petechial/purpuric rash [1][2][6]. Rapid progression necessitates immediate intravenous antibiotics (e.g., ceftriaxone, vancomycin), droplet precautions, and post-exposure prophylaxis for close contacts [1][3][16]. Vaccination (MenACWY/MenB) remains critical for prevention in high-risk populations [6][17].
Burden
Case fatality rate: 10–15%; 20% of survivors experience permanent sequelae (e.g., hearing loss, limb amputation) [6][9][11].
Global burden: 236,000 deaths (2019), with N. meningitidis contributing 13.6% of meningitis-related deaths [4].
US trends: 438 cases in 2023 (highest since 2013), driven by serogroup Y [2][17].
Therapies
Empiric IV antibiotics (ceftriaxone ± vancomycin/ampicillin) adjusted for age/risk factors [3][13].
Dexamethasone adjunct for suspected bacterial meningitis to reduce neurologic complications [3].
Post-exposure prophylaxis (rifampin, ciprofloxacin, or ceftriaxone) for close contacts and exposed healthcare workers [1][16].
Categories: rare neurological diseases
Research Papers
1,815 drug discovery papers about Meningococcal meningitis, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,815 drug discovery papers about Meningococcal meningitis, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
vaccines
2026-08-28 | Mass Gatherings as Amplifiers of Meningococcal Disease: A Modeling Study of Hajj and Umrah.
The Kingdom of Saudi Arabia (KSA) hosts millions of Hajj and Umrah pilgrims annually, and it aims to welcome 30 million external (international) Umrah pilgrims annually by 2030 (Saudi Vision 2030). These mass gatherings pose significant risks for infectious disease transmission. We extended a previous meta-population model of Neisseria meningitidis transmission during Hajj to include Umrah pilgrimage and assessed the impact of varying vaccination coverage rates (VCRs) among pilgrims on meningococcal meningitis (MM) cases. The model population was divided into five clusters: residents of the pilgrimage sites (Makkah/Madinah); the broader KSA population; and non-KSA populations from high-, medium-, and low-transmission settings. The model incorporated age, pilgrim movement patterns, and VCRs. The model was calibrated with data from 1995 to 2011 and validated with data from 2012 to 2024. MM cases under various vaccination and pilgrim scenarios were simulated for the 2025-2034 period. Umrah accounted for approximately 90% of pilgrimage days in 2023-2024, with external pilgrims accounting for > 90% of these days. In a scenario where external pilgrim numbers increased in line with Saudi Vision 2030, the probability of an annual number of MM cases exceeding 100 among pilgrims during the 2025-2034 period was estimated at 53% with a 10% VCR among internal (domestic) and external Umrah pilgrims versus < 0.02% if both VCRs were 90%. High VCRs (90%) for external and internal pilgrims reduced the number of expected MM cases across the KSA by > 80% compared with no vaccination. Our analysis highlights the amplifying effect of mass gatherings on disease transmission dynamics and confirms vaccination as a highly effective intervention. Strengthened enforcement of meningococcal ACWY vaccination requirements for all Umrah pilgrims would significantly reduce MM outbreak risk and benefit the entire KSA population, as well as the pilgrims and people in their countries of origin.
2026-08-17 | Meningitis Vaccine Delivery Strategies and Their Health Impact in Africa: A Scoping Review to Inform the Introduction of New Vaccines.
IntroductionVaccination has played a pivotal role in mitigating the burden of meningitis in the African meningitis belt. However, outbreaks have continued due to the emergence of new serogroups, and logistical barriers. This scoping review synthesizes published evidence on health impact of meningitis vaccine delivery strategies to guide policy and programmatic decision-making and maximize the impact of the new meningitis vaccines.MethodsThe review followed PRISMA extension for scoping reviews. Eligible studies published between 2004 and 2024 in English or with an English translation examining the use of meningitis vaccines and delivery strategies across Africa were included. A systematic search of online databases was conducted using predefined search terms, and following screening of 1,026 articles, 20 were included in the review. Data on relevant themes were extracted into an excel spreadsheet and analyzed guided by PAGER framework.ResultsThe review found limited real-world evidence on meningitis vaccine delivery strategies, with many studies relying on modelling approaches. Findings showed that routine infant immunization and campaign-based strategies have been used to deliver meningitis vaccines in Africa. Compared to routine vaccination, campaign-based strategies were shown to achieve high coverage rates (∼95%), high risk reduction (71%) and high decline in suspected cases (82%). However, routine immunization combined with an initial catch-up campaign was cost-effective, saving USD1.3 for every USD1 invested. The use of the Controlled Temperature Chain (CTC) system for Men A conjugate vaccines enhanced accessibility and cost-effectiveness, particularly for remote facilities lacking cold chain infrastructure. Integrated campaigns were more cost-effective than stand-alone campaigns. Combining campaigns with routine immunization resulted in significant reduction of disease burden, despite potential disruptions during mass vaccination campaigns.ConclusionsCombining routine and campaign-based immunization strategies will enhance the impact of the new meningitis vaccines. There is need for more real-world implementation and cost-effectiveness research from Africa.
2026-08-12 | Effectiveness of NmCV-5 vaccine against meningococcal meningitis in an outbreak setting in Niger: results from a case-control study.
Meningococcal meningitis remains a major public health challenge in Africa's meningitis belt despite the successful elimination of serogroup A epidemics following MenAfriVac introduction. Outbreaks caused by serogroups C, W, and X persist. NmCV-5, a pentavalent conjugate vaccine targeting serogroups A, C, W, Y, and X, was prequalified by WHO in 2023 and used in Niger during reactive vaccination campaigns in 2024. We conducted a matched case-control study in six health districts in Niger (Niamey IV and Magaria) to estimate NmCV-5 effectiveness against meningococcal meningitis. Cases were individuals with PCR-confirmed meningococcal meningitis, aged 1-19 years, resident in the vaccination campaign area, and presenting with symptom onset ≥10 days post-campaign. Enrollment took place between May 2024 and July 2025. Four age-, sex-, and residence-matched community controls were enrolled per case. Vaccination status was verified by patient-retained vaccination card when available or self-reported. Logistic regression was used to calculate crude and adjusted vaccine effectiveness (VE). 17 confirmed cases (14 NmC, 3 NmW) and 68 matched community controls were enrolled in the study. Seven cases (41%) and 58 controls (86%) reported NmCV-5 vaccination; vaccination status of all cases and 8 of 58 (14%) controls was confirmed by vaccination card. Crude VE against all meningococcal meningitis was 88% (95% CI: 62-96), and against NmC specifically was 86% (95% CI: 50-96). Adjusted for household crowding and history of recent respiratory infections, VE was 92% (95% CI: 72-98) overall and 91% (95% CI: 63-98) for NmC. Sensitivity analyses confirmed robustness of estimates under extreme assumptions. NmCV-5 demonstrated high effectiveness against circulating meningococcal strains NmC and NmW in real-world outbreak conditions. Limitations include small sample size, reliance on self-reported vaccination status, and absence of cases from other serogroups. Further studies should assess long-term impact on carriage and effectiveness against invasive disease across all targeted serogroups.
2026-08-06 | A Carriage-Structured Model of Meningococcal Meningitis: Backward Bifurcation, Seasonal Recurrence, and the Reach of Conjugate-Vaccine Strategies in the African Meningitis Belt
Epidemic meningococcal meningitis in the African meningitis belt recurs on two superimposed timescales: a sharp annual dry-season peak and irregular multi-annual epidemics separated by five to twelve years. Because invasive disease is a rare, epidemiologically dead-end outcome of asymptomatic nasopharyngeal carriage, transmission models built on the standard susceptible-infectious template misrepresent the driving process. We formulate a deterministic carriage-structured model in which only carriers transmit, immunity against carriage re-acquisition is leaky, and a conjugate vaccine protects imperfectly and wanes. We show analytically that the basic reproduction number \( R_0 \) is a property of carriage transmission and is decoupled, to first order, from disease incidence, so that reproduction numbers inferred from case notifications estimate the wrong quantity. Using the Castillo-Chavez-Song centre manifold method, we derive, in closed form, the condition for backward bifurcation and prove that it is governed by a threshold \( \varepsilon^\ast \) on carriage-blocking immunity, not by vaccine leakiness or by case-management capacity: the invasive-disease compartment is provably absent from the bifurcation condition. Under seasonal forcing we characterize, through Floquet analysis and two-parameter continuation, the region of immunity-waning and seasonal-amplitude space in which multi-annual recurrence arises, confirming that annual forcing alone cannot generate it. A scenario analysis calibrated to published belt parameter ranges quantifies the burden averted by routine infant immunisation, catch-up campaigns, and improved carriage efficacy, and shows that whether sustained immunisation eliminates epidemics or merely postpones them depends on the same carriage-efficacy threshold that governs bistability.
2026-07-28 | Recent advances in the development of a vaccine to target meningococcal serogroup X.
Serogroup X has emerged as an important cause of invasive meningococcal disease across Sub-Saharan Africa. Recent advances in serogroup X vaccines were reviewed. Early vaccine development efforts focused on outer membrane vesicle-based approaches. The growing epidemiological importance of serogroup X accelerated the development of serogroup X conjugate vaccines. Building on the success of MenAfriVac, PATH and the Serum Institute of India Pvt. Ltd. developed NmCV-5 (MenFive), the first pentavalent meningococcal conjugate vaccine targeting serogroup X. NmCV-5 achieved World Health Organization (WHO) pre-qualification in 2023, enabling deployment across Sub-Saharan Africa. A second pentavalent vaccine, EuNmCV-5, developed by Eubiologics is advancing through clinical development, while an additional candidate from Sinovac Biotech is entering early phase evaluation. These advances representative a major milestone in meningococcal disease prevention. Within the last fifteen years significant vaccine developments have been made to combat serogroup X. With NmCV-5 attaining WHO pre-qualification, strategies for its implementation within Sub-Saharan Africa are being devised. Only one vaccine is currently available in Sub- Saharan Africa, but trials of a second pentavalent ACWYX conjugate vaccine are ongoing. Carriage studies and disease surveillance are crucial to monitor serogroup X vaccine effectiveness.
small molecules
2026-09-01 | Adjunctive Corticosteroids in Pediatric Meningitis: Current Evidence, Clinical Controversies, and Future Directions
Background: Pediatric bacterial meningitis remains an important cause of death and long-term neurological disability despite advances in vaccination, antimicrobial therapy, and supportive care. Because host inflammation contributes substantially to secondary neuronal injury, adjunctive cor-ticosteroids have been investigated as a strategy to reduce inflammation-mediated complications. This narrative review aims to critically evaluate the current evidence on corticosteroid therapy in pediatric meningitis, with particular emphasis on acute bacterial meningitis, major clinical and neurological outcomes, treatment timing, pathogen-specific effects, and the impact of changing post-vaccination epidemiology. Methods: A structured search of PubMed/MEDLINE, Scopus, and Web of Science was conducted for relevant publications available up to June 2026. Randomized controlled trials, observational studies, systematic reviews, meta-analyses, and international guide-lines involving patients aged 0–18 years were considered. Evidence was synthesized narratively, focusing on mortality, hearing loss, neurological sequelae, long-term outcomes, safety, causative pathogen, and timing of corticosteroid administration. Results: Adjunctive dexamethasone does not consistently reduce mortality, hospital stay, intensive care utilization, or healthcare costs. Its most reproducible benefit is a reduction in sensorineural hearing loss, particularly in Haemophilus influ-enzae type b meningitis. Benefits in pneumococcal meningitis are less consistent, while evidence supporting routine use in meningococcal disease remains limited. Efficacy is greatest when dexa-methasone is administered before or with the first antibiotic dose and appears less pronounced in the post-vaccination era. In tuberculous meningitis, corticosteroids improve survival, whereas rou-tine use is not supported in viral or fungal meningitis. Conclusion: Current evidence supports a se-lective, pathogen- and context-specific approach to corticosteroid therapy in pediatric meningitis. Dexamethasone is best regarded as a neuroprotective adjunct, with hearing preservation repre-senting its most consistent clinical benefit.
2026-06-30 | Meningococcal serogroup W ST-11 causing meningitis, endogenous endophthalmitis, and septic arthritis in a child.
Invasive meningococcal disease (IMD) remains a major global health concern because of its epidemic potential, unpredictable presentation, and rapid progression. Although IMD classically presents as meningitis, meningococcemia, or both, Neisseria meningitidis can also cause extra-meningeal manifestations. Serogroup W (MenW), particularly the hyperinvasive ST-11 lineage, has increasingly been associated with atypical and invasive clinical phenotypes. We report an 11-year-old previously healthy boy with IMD due to MenW ST-11 who developed the exceptional triad of meningitis, endogenous endophthalmitis, and septic arthritis. An 11-year-old boy residing in a school dormitory presented with fever, rhinorrhea, cough, generalized erythematous rash, and conjunctival redness. Because of altered consciousness and seizures, he was transferred to the pediatric intensive care unit after receiving initial antibiotic therapy. He had not received meningococcal vaccines. On admission, he was lethargic, with anisocoria, marked right conjunctival hyperemia, neck stiffness, and a diffuse non-blanching petechial and purpuric rash. Cerebrospinal fluid (CSF) analysis was consistent with purulent meningitis; Gram stain showed rare Gram-negative diplococci, and CSF PCR identified N. meningitidis serogroup W, ST-11. Ophthalmologic examination confirmed severe endogenous endophthalmitis with hypopyon, and vitreous PCR also detected N. meningitidis. Because of clinical non-response with progressive ocular and neurologic involvement, therapy was escalated to meropenem. On hospital day 7, acute right knee swelling developed, and synovial fluid PCR confirmed MenW. At 6-week follow-up, the patient had normal vision, normal hearing, no neurologic deficits, and no joint sequelae. Meningococcal endophthalmitis is rare and usually associated with poor visual outcomes; only one adult MenW case has been reported previously. This case demonstrates that MenW ST-11 can cause aggressive multisystem IMD in children and underscores the importance of molecular diagnosis, early multidisciplinary care, and MenACWY vaccination.
2026-06-25 | Direct Whole-Genome Sequencing of Clinical Specimens Highlights the Emergence of Neisseria meningitidis ST-10217 in Chad.
To identify and characterize the pathogens responsible for the outbreak of invasive meningococcal disease in Chad during 2024-2025. Surveillance included demographic data and cerebrospinal fluid samples from meningitis patients. Samples were tested using RT-PCR to detect Neisseria meningitidis, Streptococcus pneumoniae, or Haemophilus influenzae. Samples positive for N. meningitidis were further analyzed by direct sequencing, with phylogenetic analysis incorporating published genomes of the same sequence types. In 2024, 12/25 samples were RT-PCR positive for S. pneumoniae. In 2025, among 65 samples, 2 were positive for H. influenzae, 12 for S. pneumoniae, and 18 for N. meningitidis; the rest were negative. Four sequence types of N. meningitidis were identified: non-groupable ST-5789 (n=1); ST-11 (n=4), associated with genogroup W; and ST-10217 (n=10) and the new ST-18990 (n=1) of the clonal complex CC10217, both genogroup C. The ST-10217 genomes had mutations in gyrA, while the ST-18990 genome possessed additionally a parC mutation, both associated with reduced ciprofloxacin susceptibility. CC10217, responsible for epidemics in Nigeria and Niger since 2015, caused a significant outbreak of serogroup C invasive meningococcal disease in Chad in 2025. The emergence of CC10217 with mutations linked to reduced ciprofloxacin susceptibility is concerning and demands close epidemiological monitoring.
2026-05-28 | Optimization of Permeable Cryoprotectants for Neisseria meningitidis Based on Assessment of Ice Inhibition and Cytotoxicity.
Neisseria meningitidis, the primary pathogen of epidemic meningococcal meningitis, is a typical fastidious bacterium with stringent nutritional requirements and high environmental sensitivity, making routine preservation challenging. Current cryopreservation methods lack quantitative efficacy evaluation and suffer from low viability. This study aimed to screen optimal permeable cryoprotectants (CPAs) for fastidious bacteria typified by N. meningitidis via cytotoxicity, cryopreservation viability, and ice crystal inhibition assays and elucidate the underlying protective mechanism. Viable cell counting with ANOVA and Tukey's test assessed the cytotoxicity and post-cryopreservation survival of N. meningitidis treated with 10/15/20% glycerol and 5%, 10%, 15% dimethyl sulfoxide (DMSO), formamide (FMD), and propylene glycol (PG) in PBS/brain heart infusion (BHI) at 37°C for 15 min and frozen at -80°C for 48 hours. Differential scanning calorimetry (DSC) analyzed thermodynamic parameters of CPA solutions, and cryomicroscopy determined ice-inhibiting properties by observing ice crystal morphology and growth rate. Cytotoxicity assays showed N. meningitidis survival rates of 88.14%, 83.85%, and 81.62% in BHI broth with 5% DMSO, 5% FMD, and 5% PG, respectively. After 48 hours of -80°C cryopreservation, 5% DMSO exhibited the best protective effect in both PBS and BHI (p < 0.05), with survival rates of 64.93% and 63.11%. DSC analysis revealed decreased crystallization enthalpy (ΔHc) and melting temperature (Tm) of DMSO with increasing concentration in BHI. Cryomicroscopy confirmed 5% DMSO most effectively inhibited ice crystal growth (921.57 μm2 in PBS, 814.20 μm2 in BHI within 50 s). 5% DMSO in BHI broth is the optimal permeable CPA for N. meningitidis and other fastidious bacteria. Its potential mechanism is that 5% DMSO balances bacterial osmotic pressure, alleviates solute and ice crystal damage, and balances ice inhibition with biocompatibility to enhance bacterial survival.
2026-05-20 | Markers of poor prognosis in meningococcal sepsis
Background. Neisseria meningitidis (meningococcus) is a highly fatal disease worldwide, occurring in epidemic and sporadic cases. The virulence of invasive N. meningitidis is determined by several key factors, including surface adhesins (pili), a protective capsule, and endotoxin release (lipid A from lipooligosaccharides). Furthermore, the bacterium has evolved genetic adaptations, including horizontal gene transfer, antigenic variation, and molecular mimicry, which allow it to successfully colonize mucosal surfaces, invade the bloodstream, and evade the immune system. The acquisition of N. meningitidis typically occurs through exposure to respiratory droplets. Meningococcal infection can present in both localized (nasopharyngitis, carriage) and generalized forms (meningitis, meningococcal bloodstream infection, meningoencephalitis, and mixed forms). Atypical presentations also include: arthritis, myocarditis, iridocyclitis, and others. The clinical form of infection is a key determinant of the outcome, the spectrum of potential complications and long-term sequelae, accounting for approximately 20-30% of cases. The epidemiology of N. meningitidis is variable and unpredictable. Early clinical symptoms are nonspecific and can lead to misdiagnosis and, therefore, delayed optimal treatment. Objective. To analyze clinical and laboratory data to identify the clinical features and markers of adverse events in meningococcal sepsis (meningococcemia). Materials and methods. We analyzed the records of inpatients under 18 years of age treated for meningococcemia (meningococcal sepsis) at the Minsk City Children's Infectious Diseases Clinical Hospital from 2009 to 2024. Results. The main clinical manifestations of meningococcal sepsis are febrile fever (98.1-100%) and rash (100%). Meningococcemia most often occurs in combination with nervous system damage and the development of meningitis/meningoencephalitis (53.2-69.3%). The development of Waterhouse-Friderichsen syndrome in meningococcal sepsis increases the risk of death by almost 9 times. Conclusion. Established markers of an unfavorable course of meningococcal sepsis include septic shock and Waterhouse-Friderichsen syndrome.
proteins
2026-09-15 | Developing a novel chimeric antimicrobial peptide for the treatment of central nervous system bacterial infections
Bacterial meningitis remains a life-threatening central nervous system (CNS) infection with a high mortality rate and long-term neurological sequelae, largely due to the limited ability of most antimicrobials to cross the blood–brain barrier (BBB). Here, we report the rational design of a BBB-targeted chimeric antimicrobial peptide, P-FK5-X-TGN, that combines a palmitoylated random peptide mixture (P-FK5) with the BBB-homing peptide TGN via a flexible hexanoic acid linker (X). The chimeric peptide retained potent antibacterial activity against Neisseria meningitidis (MIC 8 µg/ml) and demonstrated efficient traversal of an in vitro BBB model, reducing bacterial viability better than unconjugated P-FK5 and ciprofloxacin. In a murine model of meningococcal infection, P-FK5-X-TGN was well tolerated and improved survival (67%) compared to P-FK5 (0%) and ciprofloxacin (50%), despite being administered at a 5-fold lower dose. Importantly, treatment with P-FK5-X-TGN also resulted in a ~ 3-log reduction in bacterial burden in the brain. Collectively, these results establish BBB-targeted antimicrobial peptides as an interesting noninvasive strategy for the treatment of CNS infections and highlight P-FK5-X-TGN as a proof-of-concept therapeutic for bacterial meningitis for further studies.
2024-09-04 | Angiopoietin-like 4 protects against endothelial dysfunction during bacterial sepsis.
Loss of endothelial integrity and vascular leakage are central features of sepsis pathogenesis; however, no effective therapeutic mechanisms for preserving endothelial integrity are available. Here we show that, compared to dermal microvessels, brain microvessels resist infection by Neisseria meningitidis, a bacterial pathogen that causes sepsis and meningitis. By comparing the transcriptional responses to infection in dermal and brain endothelial cells, we identified angiopoietin-like 4 as a key factor produced by the brain endothelium that preserves blood-brain barrier integrity during bacterial sepsis. Conversely, angiopoietin-like 4 is produced at lower levels in the peripheral endothelium. Treatment with recombinant angiopoietin-like 4 reduced vascular leakage, organ failure and death in mouse models of lethal sepsis and N. meningitidis infection. Protection was conferred by a previously uncharacterized domain of angiopoietin-like 4, through binding to the heparan proteoglycan, syndecan-4. These findings reveal a potential strategy to prevent endothelial dysfunction and improve outcomes in patients with sepsis.
2022-09-23 | Specific Antibodies to the Fragments of Meningococcal IgA1 Protease during the Formation of Immunity to Bacterial Infections.
The features of individual fragments of IgA1 protease of Neisseria meningitidis serogroup B during the formation of immunity to bacterial infections in animals and humans were studied. The antibodies to the immunogenic regions of the studied proteins are also detected in mice infected with some bacterial pathogens and in humans with bacterial meningitis. A region of IgA1 protease was identified that is not capable of producing antibodies during immunization of animals, but that detects homologous antibodies in the blood of humans and animals recovered from bacterial infections. It has been suggested that this fragment plays a regulatory role in the process of immunogenesis.
2021-02-08 | Loss of Factor H family proteins associates with meningococcal disease severity
ABSTRACT Neisseria meningitidis , the causative agent of meningococcal disease (MD), evades complement-mediated clearance upon infection by ‘hijacking’ the human complement regulator factor H (FH). The FH protein family also comprises the homologous FH-related (FHR) proteins, hypothesized to act as antagonists of FH, and FHR-3 has recently been implicated to play a major role in MD susceptibility. Here, we show that, next to FH and FHR-3, the circulating levels of all FH family proteins are equally decreased during pediatric MD. We did not observe a specific consumption of FH or FHR-3 by N. meningitidis during the first days of infection and the levels recovered over time. MD severity associated predominantly with a loss of FH. Strikingly, loss of FH and FHRs associated strongly with renal failure, suggesting insufficient protection of host tissue by the FH protein family. Retaining higher levels of FH family proteins may thus limit tissue injury during MD.
2019-12-02 | Immunoenhancement of Recombinant Neisseria meningitides PorB Protein on Porcine Circovirus Type 2 and Mycoplasma hyopneumoniae Genetically Engineered Vaccines.
Porcine circovirus and Mycoplasma hyopneumoniae can cause respiratory diseases in pigs, which cause serious economic loss in the worldwide pig industry. Currently, these infections are mainly prevented and controlled by vaccination. The new vaccines on the market are mainly composed of subunits and inactivated vaccines but usually have lower antigenicity than traditional live vaccines. Thus, there is an increasing need to develop new adjuvants that can cause rapid and long-lasting immunity to enhance the antigenic efficacy for vaccines. Studies have shown that meningococcal porin PorB can act as a ligand to combine with Toll-like receptors to activate the production of immunological projections and act as a vaccine immunological adjuvant. In this article, we expressed and purified the recombinant PorB protein and verified its immunogenicity against porcine circovirus type 2 and Mycoplasma hyopneumoniae genetically engineered vaccine. In this article, we used prokaryotic expression to express and purify recombinant PorB protein, four different concentrations of PorB protein, Freund's adjuvant with two genetically engineered vaccines were combined with subcutaneous immunization of mice. Our study shows that the appropriate dose of the recombinant protein PorB can enhance the levels of humoral and cellular responses induced by two genetically engineered vaccines in a short period of time in mice. The PorB adjuvant group may cause statistically higher antibody titers for both genetically engineered vaccines compared to Freund's commercial adjuvant (P<0.001). The recombinant protein PorB may be a good candidate adjuvant for improving the protective effect of vaccines against porcine circovirus type 2 and Mycoplasma hyopneumoniae, and the protein can be used for future practical applications.
oligonucleotides
2023-01-16 | Tracing the Negative Results of Multiplex Real-Time PCR Assay for Diagnosis of Bacterial Pediatrics Meningitis
The death because of meningitis remains high in some parts of the world. It is important to know the specific cause of meningitis because the treatment differs depending on the cause. This study aimed to trace the false-negative results of multiplex RT-PCR to detect Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis serogroup by two different molecular methods. In this study, the CSF of the suspicious pediatric for acute bacterial meningitis among children aged 1 month to 14 years who are admitted to the hospitals in four cities of a certain region of Iran was collected. S. pneumoniae, H. influenzae, and N. meningitidis in CSF samples were detected by single-tube multiplex RT-PCR and specific RT-PCR with a probe on the same specimens. In this cross-sectional study, 506 CSF samples were collected during one year. The multiplex RT-PCR can detect 3.3% and 2.2% of S. pneumoniae and H. influenzae, respectively. N. meningitidis was not detected. The CSF analysis was abnormal in 53% of 506 patients. On the other hand, 11.5%, 4.8%, and 4.1% of S. pneumoniae, H. influenzae, and N. meningitidis were identified, respectively, by specific RT-PCR assay, exactly on the same specimens. Various types of PCR can be used for pathogen identification. As we change the type of PCR in our study, we could approximately increase 15% our positive results and also consequently decrease our false-negative responses.
2021-04-07 | Quality of metagenomic DNA extracted for molecular identification of microorganisms from CSF samples of patients with suspected cerebrospinal meningitis in northern Nigeria
Background: Following an increase in the practice of starting antimicrobial therapy prior to clinical sample collection, the ability to confirm pathogenic microorganisms of bacterial meningitis has decreased by approximately 30%. Culture results may be false negative when fastidious or culture-resistant bacteria are involved or when patient samples are obtained after antimicrobial therapy has started. Molecular diagnosis using PCR can be performed directly on clinical samples after metagenomic DNA (mDNA) extraction not requiring live organisms for a positive result. The specific objectives of this study are to perform mDNA extraction directly from cerebrospinal fluids (CSF) using appropriate spin column method, and to determine the quality of the mDNA elute.Methodology: Cerebrospinal fluid specimens were collected from 210 patients with suspected acute cerebrospinal meningitis (CSM) in the Federal Capital Territory and some States in Northern Nigeria during the 2017 and 2018 outbreak seasons. Metagenomic DNA was extracted from approximately 200µL of CSF specimens using the Qiagen QIAamp(R) DNA Mini kit specific for bacterial agents only. DNA quality check was performed on all DNA elutes using fluorometric, spectrophotometric and agarose gel electrophoresis methods.Results: Of the 210 CSF samples analyzed microbiologically, Gram reaction was positive in 94 cases (44.8 %) but only 17 (8.1 %) were culture positive for two of the three major bacterial causes of meningitis. One hundred and eighty (85.7%) samples had DNA concentrations ≥ 0.005 ng/µL, 55 (30.6 %) of these had DNA purity (A260/A280) of ≥ 1.7, 103 (57.2%) had purity value between 1.0 - 1.69, 14 (7.8%) had value of 0.57 - 0.99, and 8 (4.4%) failed purity evaluation with value of 0.00 at A260/A280.Conclusion: The essence of mDNA extraction is multipurpose. A multiplex PCR can be performed on the extracted mDNA to interrogate the presence of microbial pathogens of interest using specific primers and probes (when applicable). Quality mDNA from CSF samples will ensure successful qPCR results for rapid and accurate detection of bacterial pathogens in meningitis. This will eliminate the challenges associated with traditional culture methods. Keywords: Meningitis, CSF, DNA Quality Check, Fluorometry
2020-09-17 | A homopolymeric adenosine tract in the promoter region of nspA influences factor H-mediated serum resistance in Neisseria meningitidis.
Although usually asymptomatically colonizing the human nasopharynx, the Gram-negative bacterium Neisseria meningitidis (meningococcus) can spread to the blood stream and cause invasive disease. For survival in blood, N. meningitidis evades the complement system by expression of a polysaccharide capsule and surface proteins sequestering the complement regulator factor H (fH). Meningococcal strains belonging to the sequence type (ST-) 41/44 clonal complex (cc41/44) cause a major proportion of serogroup B meningococcal disease worldwide, but they are also common in asymptomatic carriers. Proteome analysis comparing cc41/44 isolates from invasive disease versus carriage revealed differential expression levels of the outer membrane protein NspA, which binds fH. Deletion of nspA reduced serum resistance and NspA expression correlated with fH sequestration. Expression levels of NspA depended on the length of a homopolymeric tract in the nspA promoter: A 5-adenosine tract dictated low NspA expression, whereas a 6-adenosine motif guided high NspA expression. Screening German cc41/44 strain collections revealed the 6-adenosine motif in 39% of disease isolates, but only in 3.4% of carriage isolates. Thus, high NspA expression is associated with disease, but not strictly required. The 6-adenosine nspA promoter is most common to the cc41/44, but is also found in other hypervirulent clonal complexes.
2014-05-27 | Lipopolysaccharide engineering in Neisseria meningitidis: structural analysis of different pentaacyl lipid A mutants and comparison of their modified agonist properties.
Engineering the lipopolysaccharide (LPS) biosynthetic pathway offers the potential to obtain modified derivatives with optimized adjuvant properties. Neisseria meningitidis strain H44/76 was modified by expression of the pagL gene encoding lipid A 3-O-deacylase from Bordetella bronchiseptica and by inactivation of the lgtB gene encoding the terminal oligosaccharide galactosyltransferase. Mass spectrometry analysis of purified mutant LPS was used for detailed compositional analysis of all present molecular species. This determined that the modified LPS was mainly pentaacylated, demonstrating high efficiency of conversion from the hexaacyl to the 3-O-deacylated form by heterologous lipid A 3-O-deacylase (PagL) expression. MS analyses also provided evidence for expression of only one major oligosaccharide glycoform, which lacked the terminal galactose residue as expected from inactivation of the lgtB gene. The immunomodulatory properties of PagL-deacylated LPS were compared with another pentaacyl form obtained from an lpxL1(-) mutant, which lacks the 2' secondary acyl chain. Although both LPS mutants displayed impaired capacity to induce production of the pro-inflammatory cytokine IL-6 in the monocytic cell line Mono Mac 6, induction of the Toll-interleukin-1 receptor domain-containing adaptor-inducing interferon-β-dependent chemokine interferon-γ-induced protein 10 was largely retained only for the lgtB(-)/pagL(+) mutant. Removal of remaining hexaacyl species exclusively present in lgtB(-)/pagL(+) LPS demonstrated that these minor species potentiate but do not determine the activity of this LPS. These results are the first to indicate a qualitatively different response of human innate cells to pentaacyl lpxL1(-) and pagL(+) LPS and show the importance of detailed structure-function analysis when working with modified lipid A structures. The pagL(+) LPS has significant potential as immune modulator in humans.
2003-09-18 | Induction of a protective capsular polysaccharide antibody response to a multiepitope DNA vaccine encoding a peptide mimic of meningococcal serogroup C capsular polysaccharide
Summary Systemic infection by encapsulated organisms, such as Neisseria meningitidis , is a major cause of morbidity and mortality worldwide, especially in individuals less than 2 years of age. Antibodies directed at the capsular polysaccharide are shown to be protective against disease by inducing complement‐dependent bactericidal activity. The current polysaccharide vaccine has been shown to be poorly immunogenic in high‐risk groups and this is probably related to its T‐independent properties. An alternative approach to eliciting a T‐dependent serum immunoglobulin G (IgG) antibody response to encapsulated pathogens is DNA vaccination. We assessed the immunogenicity of a multiepitope DNA vaccine encoding a T‐cell helper epitope and a peptide mimic of N. meningitidis serogroup C. The DNA construct induced a significant anti‐polysaccharide antibody response that was bactericidal. Mice immunized with the DNA construct were subsequently protected against challenge with a lethal dose of N. meningitidis serogroup C.
vaccines
2026-08-28 | Mass Gatherings as Amplifiers of Meningococcal Disease: A Modeling Study of Hajj and Umrah.
The Kingdom of Saudi Arabia (KSA) hosts millions of Hajj and Umrah pilgrims annually, and it aims to welcome 30 million external (international) Umrah pilgrims annually by 2030 (Saudi Vision 2030). These mass gatherings pose significant risks for infectious disease transmission. We extended a previous meta-population model of Neisseria meningitidis transmission during Hajj to include Umrah pilgrimage and assessed the impact of varying vaccination coverage rates (VCRs) among pilgrims on meningococcal meningitis (MM) cases. The model population was divided into five clusters: residents of the pilgrimage sites (Makkah/Madinah); the broader KSA population; and non-KSA populations from high-, medium-, and low-transmission settings. The model incorporated age, pilgrim movement patterns, and VCRs. The model was calibrated with data from 1995 to 2011 and validated with data from 2012 to 2024. MM cases under various vaccination and pilgrim scenarios were simulated for the 2025-2034 period. Umrah accounted for approximately 90% of pilgrimage days in 2023-2024, with external pilgrims accounting for > 90% of these days. In a scenario where external pilgrim numbers increased in line with Saudi Vision 2030, the probability of an annual number of MM cases exceeding 100 among pilgrims during the 2025-2034 period was estimated at 53% with a 10% VCR among internal (domestic) and external Umrah pilgrims versus < 0.02% if both VCRs were 90%. High VCRs (90%) for external and internal pilgrims reduced the number of expected MM cases across the KSA by > 80% compared with no vaccination. Our analysis highlights the amplifying effect of mass gatherings on disease transmission dynamics and confirms vaccination as a highly effective intervention. Strengthened enforcement of meningococcal ACWY vaccination requirements for all Umrah pilgrims would significantly reduce MM outbreak risk and benefit the entire KSA population, as well as the pilgrims and people in their countries of origin.
2026-08-17 | Meningitis Vaccine Delivery Strategies and Their Health Impact in Africa: A Scoping Review to Inform the Introduction of New Vaccines.
IntroductionVaccination has played a pivotal role in mitigating the burden of meningitis in the African meningitis belt. However, outbreaks have continued due to the emergence of new serogroups, and logistical barriers. This scoping review synthesizes published evidence on health impact of meningitis vaccine delivery strategies to guide policy and programmatic decision-making and maximize the impact of the new meningitis vaccines.MethodsThe review followed PRISMA extension for scoping reviews. Eligible studies published between 2004 and 2024 in English or with an English translation examining the use of meningitis vaccines and delivery strategies across Africa were included. A systematic search of online databases was conducted using predefined search terms, and following screening of 1,026 articles, 20 were included in the review. Data on relevant themes were extracted into an excel spreadsheet and analyzed guided by PAGER framework.ResultsThe review found limited real-world evidence on meningitis vaccine delivery strategies, with many studies relying on modelling approaches. Findings showed that routine infant immunization and campaign-based strategies have been used to deliver meningitis vaccines in Africa. Compared to routine vaccination, campaign-based strategies were shown to achieve high coverage rates (∼95%), high risk reduction (71%) and high decline in suspected cases (82%). However, routine immunization combined with an initial catch-up campaign was cost-effective, saving USD1.3 for every USD1 invested. The use of the Controlled Temperature Chain (CTC) system for Men A conjugate vaccines enhanced accessibility and cost-effectiveness, particularly for remote facilities lacking cold chain infrastructure. Integrated campaigns were more cost-effective than stand-alone campaigns. Combining campaigns with routine immunization resulted in significant reduction of disease burden, despite potential disruptions during mass vaccination campaigns.ConclusionsCombining routine and campaign-based immunization strategies will enhance the impact of the new meningitis vaccines. There is need for more real-world implementation and cost-effectiveness research from Africa.
2026-08-12 | Effectiveness of NmCV-5 vaccine against meningococcal meningitis in an outbreak setting in Niger: results from a case-control study.
Meningococcal meningitis remains a major public health challenge in Africa's meningitis belt despite the successful elimination of serogroup A epidemics following MenAfriVac introduction. Outbreaks caused by serogroups C, W, and X persist. NmCV-5, a pentavalent conjugate vaccine targeting serogroups A, C, W, Y, and X, was prequalified by WHO in 2023 and used in Niger during reactive vaccination campaigns in 2024. We conducted a matched case-control study in six health districts in Niger (Niamey IV and Magaria) to estimate NmCV-5 effectiveness against meningococcal meningitis. Cases were individuals with PCR-confirmed meningococcal meningitis, aged 1-19 years, resident in the vaccination campaign area, and presenting with symptom onset ≥10 days post-campaign. Enrollment took place between May 2024 and July 2025. Four age-, sex-, and residence-matched community controls were enrolled per case. Vaccination status was verified by patient-retained vaccination card when available or self-reported. Logistic regression was used to calculate crude and adjusted vaccine effectiveness (VE). 17 confirmed cases (14 NmC, 3 NmW) and 68 matched community controls were enrolled in the study. Seven cases (41%) and 58 controls (86%) reported NmCV-5 vaccination; vaccination status of all cases and 8 of 58 (14%) controls was confirmed by vaccination card. Crude VE against all meningococcal meningitis was 88% (95% CI: 62-96), and against NmC specifically was 86% (95% CI: 50-96). Adjusted for household crowding and history of recent respiratory infections, VE was 92% (95% CI: 72-98) overall and 91% (95% CI: 63-98) for NmC. Sensitivity analyses confirmed robustness of estimates under extreme assumptions. NmCV-5 demonstrated high effectiveness against circulating meningococcal strains NmC and NmW in real-world outbreak conditions. Limitations include small sample size, reliance on self-reported vaccination status, and absence of cases from other serogroups. Further studies should assess long-term impact on carriage and effectiveness against invasive disease across all targeted serogroups.
2026-08-06 | A Carriage-Structured Model of Meningococcal Meningitis: Backward Bifurcation, Seasonal Recurrence, and the Reach of Conjugate-Vaccine Strategies in the African Meningitis Belt
Epidemic meningococcal meningitis in the African meningitis belt recurs on two superimposed timescales: a sharp annual dry-season peak and irregular multi-annual epidemics separated by five to twelve years. Because invasive disease is a rare, epidemiologically dead-end outcome of asymptomatic nasopharyngeal carriage, transmission models built on the standard susceptible-infectious template misrepresent the driving process. We formulate a deterministic carriage-structured model in which only carriers transmit, immunity against carriage re-acquisition is leaky, and a conjugate vaccine protects imperfectly and wanes. We show analytically that the basic reproduction number \( R_0 \) is a property of carriage transmission and is decoupled, to first order, from disease incidence, so that reproduction numbers inferred from case notifications estimate the wrong quantity. Using the Castillo-Chavez-Song centre manifold method, we derive, in closed form, the condition for backward bifurcation and prove that it is governed by a threshold \( \varepsilon^\ast \) on carriage-blocking immunity, not by vaccine leakiness or by case-management capacity: the invasive-disease compartment is provably absent from the bifurcation condition. Under seasonal forcing we characterize, through Floquet analysis and two-parameter continuation, the region of immunity-waning and seasonal-amplitude space in which multi-annual recurrence arises, confirming that annual forcing alone cannot generate it. A scenario analysis calibrated to published belt parameter ranges quantifies the burden averted by routine infant immunisation, catch-up campaigns, and improved carriage efficacy, and shows that whether sustained immunisation eliminates epidemics or merely postpones them depends on the same carriage-efficacy threshold that governs bistability.
2026-07-28 | Recent advances in the development of a vaccine to target meningococcal serogroup X.
Serogroup X has emerged as an important cause of invasive meningococcal disease across Sub-Saharan Africa. Recent advances in serogroup X vaccines were reviewed. Early vaccine development efforts focused on outer membrane vesicle-based approaches. The growing epidemiological importance of serogroup X accelerated the development of serogroup X conjugate vaccines. Building on the success of MenAfriVac, PATH and the Serum Institute of India Pvt. Ltd. developed NmCV-5 (MenFive), the first pentavalent meningococcal conjugate vaccine targeting serogroup X. NmCV-5 achieved World Health Organization (WHO) pre-qualification in 2023, enabling deployment across Sub-Saharan Africa. A second pentavalent vaccine, EuNmCV-5, developed by Eubiologics is advancing through clinical development, while an additional candidate from Sinovac Biotech is entering early phase evaluation. These advances representative a major milestone in meningococcal disease prevention. Within the last fifteen years significant vaccine developments have been made to combat serogroup X. With NmCV-5 attaining WHO pre-qualification, strategies for its implementation within Sub-Saharan Africa are being devised. Only one vaccine is currently available in Sub- Saharan Africa, but trials of a second pentavalent ACWYX conjugate vaccine are ongoing. Carriage studies and disease surveillance are crucial to monitor serogroup X vaccine effectiveness.
small molecules
2026-09-01 | Adjunctive Corticosteroids in Pediatric Meningitis: Current Evidence, Clinical Controversies, and Future Directions
Background: Pediatric bacterial meningitis remains an important cause of death and long-term neurological disability despite advances in vaccination, antimicrobial therapy, and supportive care. Because host inflammation contributes substantially to secondary neuronal injury, adjunctive cor-ticosteroids have been investigated as a strategy to reduce inflammation-mediated complications. This narrative review aims to critically evaluate the current evidence on corticosteroid therapy in pediatric meningitis, with particular emphasis on acute bacterial meningitis, major clinical and neurological outcomes, treatment timing, pathogen-specific effects, and the impact of changing post-vaccination epidemiology. Methods: A structured search of PubMed/MEDLINE, Scopus, and Web of Science was conducted for relevant publications available up to June 2026. Randomized controlled trials, observational studies, systematic reviews, meta-analyses, and international guide-lines involving patients aged 0–18 years were considered. Evidence was synthesized narratively, focusing on mortality, hearing loss, neurological sequelae, long-term outcomes, safety, causative pathogen, and timing of corticosteroid administration. Results: Adjunctive dexamethasone does not consistently reduce mortality, hospital stay, intensive care utilization, or healthcare costs. Its most reproducible benefit is a reduction in sensorineural hearing loss, particularly in Haemophilus influ-enzae type b meningitis. Benefits in pneumococcal meningitis are less consistent, while evidence supporting routine use in meningococcal disease remains limited. Efficacy is greatest when dexa-methasone is administered before or with the first antibiotic dose and appears less pronounced in the post-vaccination era. In tuberculous meningitis, corticosteroids improve survival, whereas rou-tine use is not supported in viral or fungal meningitis. Conclusion: Current evidence supports a se-lective, pathogen- and context-specific approach to corticosteroid therapy in pediatric meningitis. Dexamethasone is best regarded as a neuroprotective adjunct, with hearing preservation repre-senting its most consistent clinical benefit.
2026-06-30 | Meningococcal serogroup W ST-11 causing meningitis, endogenous endophthalmitis, and septic arthritis in a child.
Invasive meningococcal disease (IMD) remains a major global health concern because of its epidemic potential, unpredictable presentation, and rapid progression. Although IMD classically presents as meningitis, meningococcemia, or both, Neisseria meningitidis can also cause extra-meningeal manifestations. Serogroup W (MenW), particularly the hyperinvasive ST-11 lineage, has increasingly been associated with atypical and invasive clinical phenotypes. We report an 11-year-old previously healthy boy with IMD due to MenW ST-11 who developed the exceptional triad of meningitis, endogenous endophthalmitis, and septic arthritis. An 11-year-old boy residing in a school dormitory presented with fever, rhinorrhea, cough, generalized erythematous rash, and conjunctival redness. Because of altered consciousness and seizures, he was transferred to the pediatric intensive care unit after receiving initial antibiotic therapy. He had not received meningococcal vaccines. On admission, he was lethargic, with anisocoria, marked right conjunctival hyperemia, neck stiffness, and a diffuse non-blanching petechial and purpuric rash. Cerebrospinal fluid (CSF) analysis was consistent with purulent meningitis; Gram stain showed rare Gram-negative diplococci, and CSF PCR identified N. meningitidis serogroup W, ST-11. Ophthalmologic examination confirmed severe endogenous endophthalmitis with hypopyon, and vitreous PCR also detected N. meningitidis. Because of clinical non-response with progressive ocular and neurologic involvement, therapy was escalated to meropenem. On hospital day 7, acute right knee swelling developed, and synovial fluid PCR confirmed MenW. At 6-week follow-up, the patient had normal vision, normal hearing, no neurologic deficits, and no joint sequelae. Meningococcal endophthalmitis is rare and usually associated with poor visual outcomes; only one adult MenW case has been reported previously. This case demonstrates that MenW ST-11 can cause aggressive multisystem IMD in children and underscores the importance of molecular diagnosis, early multidisciplinary care, and MenACWY vaccination.
2026-06-25 | Direct Whole-Genome Sequencing of Clinical Specimens Highlights the Emergence of Neisseria meningitidis ST-10217 in Chad.
To identify and characterize the pathogens responsible for the outbreak of invasive meningococcal disease in Chad during 2024-2025. Surveillance included demographic data and cerebrospinal fluid samples from meningitis patients. Samples were tested using RT-PCR to detect Neisseria meningitidis, Streptococcus pneumoniae, or Haemophilus influenzae. Samples positive for N. meningitidis were further analyzed by direct sequencing, with phylogenetic analysis incorporating published genomes of the same sequence types. In 2024, 12/25 samples were RT-PCR positive for S. pneumoniae. In 2025, among 65 samples, 2 were positive for H. influenzae, 12 for S. pneumoniae, and 18 for N. meningitidis; the rest were negative. Four sequence types of N. meningitidis were identified: non-groupable ST-5789 (n=1); ST-11 (n=4), associated with genogroup W; and ST-10217 (n=10) and the new ST-18990 (n=1) of the clonal complex CC10217, both genogroup C. The ST-10217 genomes had mutations in gyrA, while the ST-18990 genome possessed additionally a parC mutation, both associated with reduced ciprofloxacin susceptibility. CC10217, responsible for epidemics in Nigeria and Niger since 2015, caused a significant outbreak of serogroup C invasive meningococcal disease in Chad in 2025. The emergence of CC10217 with mutations linked to reduced ciprofloxacin susceptibility is concerning and demands close epidemiological monitoring.
2026-05-28 | Optimization of Permeable Cryoprotectants for Neisseria meningitidis Based on Assessment of Ice Inhibition and Cytotoxicity.
Neisseria meningitidis, the primary pathogen of epidemic meningococcal meningitis, is a typical fastidious bacterium with stringent nutritional requirements and high environmental sensitivity, making routine preservation challenging. Current cryopreservation methods lack quantitative efficacy evaluation and suffer from low viability. This study aimed to screen optimal permeable cryoprotectants (CPAs) for fastidious bacteria typified by N. meningitidis via cytotoxicity, cryopreservation viability, and ice crystal inhibition assays and elucidate the underlying protective mechanism. Viable cell counting with ANOVA and Tukey's test assessed the cytotoxicity and post-cryopreservation survival of N. meningitidis treated with 10/15/20% glycerol and 5%, 10%, 15% dimethyl sulfoxide (DMSO), formamide (FMD), and propylene glycol (PG) in PBS/brain heart infusion (BHI) at 37°C for 15 min and frozen at -80°C for 48 hours. Differential scanning calorimetry (DSC) analyzed thermodynamic parameters of CPA solutions, and cryomicroscopy determined ice-inhibiting properties by observing ice crystal morphology and growth rate. Cytotoxicity assays showed N. meningitidis survival rates of 88.14%, 83.85%, and 81.62% in BHI broth with 5% DMSO, 5% FMD, and 5% PG, respectively. After 48 hours of -80°C cryopreservation, 5% DMSO exhibited the best protective effect in both PBS and BHI (p < 0.05), with survival rates of 64.93% and 63.11%. DSC analysis revealed decreased crystallization enthalpy (ΔHc) and melting temperature (Tm) of DMSO with increasing concentration in BHI. Cryomicroscopy confirmed 5% DMSO most effectively inhibited ice crystal growth (921.57 μm2 in PBS, 814.20 μm2 in BHI within 50 s). 5% DMSO in BHI broth is the optimal permeable CPA for N. meningitidis and other fastidious bacteria. Its potential mechanism is that 5% DMSO balances bacterial osmotic pressure, alleviates solute and ice crystal damage, and balances ice inhibition with biocompatibility to enhance bacterial survival.
2026-05-20 | Markers of poor prognosis in meningococcal sepsis
Background. Neisseria meningitidis (meningococcus) is a highly fatal disease worldwide, occurring in epidemic and sporadic cases. The virulence of invasive N. meningitidis is determined by several key factors, including surface adhesins (pili), a protective capsule, and endotoxin release (lipid A from lipooligosaccharides). Furthermore, the bacterium has evolved genetic adaptations, including horizontal gene transfer, antigenic variation, and molecular mimicry, which allow it to successfully colonize mucosal surfaces, invade the bloodstream, and evade the immune system. The acquisition of N. meningitidis typically occurs through exposure to respiratory droplets. Meningococcal infection can present in both localized (nasopharyngitis, carriage) and generalized forms (meningitis, meningococcal bloodstream infection, meningoencephalitis, and mixed forms). Atypical presentations also include: arthritis, myocarditis, iridocyclitis, and others. The clinical form of infection is a key determinant of the outcome, the spectrum of potential complications and long-term sequelae, accounting for approximately 20-30% of cases. The epidemiology of N. meningitidis is variable and unpredictable. Early clinical symptoms are nonspecific and can lead to misdiagnosis and, therefore, delayed optimal treatment. Objective. To analyze clinical and laboratory data to identify the clinical features and markers of adverse events in meningococcal sepsis (meningococcemia). Materials and methods. We analyzed the records of inpatients under 18 years of age treated for meningococcemia (meningococcal sepsis) at the Minsk City Children's Infectious Diseases Clinical Hospital from 2009 to 2024. Results. The main clinical manifestations of meningococcal sepsis are febrile fever (98.1-100%) and rash (100%). Meningococcemia most often occurs in combination with nervous system damage and the development of meningitis/meningoencephalitis (53.2-69.3%). The development of Waterhouse-Friderichsen syndrome in meningococcal sepsis increases the risk of death by almost 9 times. Conclusion. Established markers of an unfavorable course of meningococcal sepsis include septic shock and Waterhouse-Friderichsen syndrome.
proteins
2026-09-15 | Developing a novel chimeric antimicrobial peptide for the treatment of central nervous system bacterial infections
Bacterial meningitis remains a life-threatening central nervous system (CNS) infection with a high mortality rate and long-term neurological sequelae, largely due to the limited ability of most antimicrobials to cross the blood–brain barrier (BBB). Here, we report the rational design of a BBB-targeted chimeric antimicrobial peptide, P-FK5-X-TGN, that combines a palmitoylated random peptide mixture (P-FK5) with the BBB-homing peptide TGN via a flexible hexanoic acid linker (X). The chimeric peptide retained potent antibacterial activity against Neisseria meningitidis (MIC 8 µg/ml) and demonstrated efficient traversal of an in vitro BBB model, reducing bacterial viability better than unconjugated P-FK5 and ciprofloxacin. In a murine model of meningococcal infection, P-FK5-X-TGN was well tolerated and improved survival (67%) compared to P-FK5 (0%) and ciprofloxacin (50%), despite being administered at a 5-fold lower dose. Importantly, treatment with P-FK5-X-TGN also resulted in a ~ 3-log reduction in bacterial burden in the brain. Collectively, these results establish BBB-targeted antimicrobial peptides as an interesting noninvasive strategy for the treatment of CNS infections and highlight P-FK5-X-TGN as a proof-of-concept therapeutic for bacterial meningitis for further studies.
2024-09-04 | Angiopoietin-like 4 protects against endothelial dysfunction during bacterial sepsis.
Loss of endothelial integrity and vascular leakage are central features of sepsis pathogenesis; however, no effective therapeutic mechanisms for preserving endothelial integrity are available. Here we show that, compared to dermal microvessels, brain microvessels resist infection by Neisseria meningitidis, a bacterial pathogen that causes sepsis and meningitis. By comparing the transcriptional responses to infection in dermal and brain endothelial cells, we identified angiopoietin-like 4 as a key factor produced by the brain endothelium that preserves blood-brain barrier integrity during bacterial sepsis. Conversely, angiopoietin-like 4 is produced at lower levels in the peripheral endothelium. Treatment with recombinant angiopoietin-like 4 reduced vascular leakage, organ failure and death in mouse models of lethal sepsis and N. meningitidis infection. Protection was conferred by a previously uncharacterized domain of angiopoietin-like 4, through binding to the heparan proteoglycan, syndecan-4. These findings reveal a potential strategy to prevent endothelial dysfunction and improve outcomes in patients with sepsis.
2022-09-23 | Specific Antibodies to the Fragments of Meningococcal IgA1 Protease during the Formation of Immunity to Bacterial Infections.
The features of individual fragments of IgA1 protease of Neisseria meningitidis serogroup B during the formation of immunity to bacterial infections in animals and humans were studied. The antibodies to the immunogenic regions of the studied proteins are also detected in mice infected with some bacterial pathogens and in humans with bacterial meningitis. A region of IgA1 protease was identified that is not capable of producing antibodies during immunization of animals, but that detects homologous antibodies in the blood of humans and animals recovered from bacterial infections. It has been suggested that this fragment plays a regulatory role in the process of immunogenesis.
2021-02-08 | Loss of Factor H family proteins associates with meningococcal disease severity
ABSTRACT Neisseria meningitidis , the causative agent of meningococcal disease (MD), evades complement-mediated clearance upon infection by ‘hijacking’ the human complement regulator factor H (FH). The FH protein family also comprises the homologous FH-related (FHR) proteins, hypothesized to act as antagonists of FH, and FHR-3 has recently been implicated to play a major role in MD susceptibility. Here, we show that, next to FH and FHR-3, the circulating levels of all FH family proteins are equally decreased during pediatric MD. We did not observe a specific consumption of FH or FHR-3 by N. meningitidis during the first days of infection and the levels recovered over time. MD severity associated predominantly with a loss of FH. Strikingly, loss of FH and FHRs associated strongly with renal failure, suggesting insufficient protection of host tissue by the FH protein family. Retaining higher levels of FH family proteins may thus limit tissue injury during MD.
2019-12-02 | Immunoenhancement of Recombinant Neisseria meningitides PorB Protein on Porcine Circovirus Type 2 and Mycoplasma hyopneumoniae Genetically Engineered Vaccines.
Porcine circovirus and Mycoplasma hyopneumoniae can cause respiratory diseases in pigs, which cause serious economic loss in the worldwide pig industry. Currently, these infections are mainly prevented and controlled by vaccination. The new vaccines on the market are mainly composed of subunits and inactivated vaccines but usually have lower antigenicity than traditional live vaccines. Thus, there is an increasing need to develop new adjuvants that can cause rapid and long-lasting immunity to enhance the antigenic efficacy for vaccines. Studies have shown that meningococcal porin PorB can act as a ligand to combine with Toll-like receptors to activate the production of immunological projections and act as a vaccine immunological adjuvant. In this article, we expressed and purified the recombinant PorB protein and verified its immunogenicity against porcine circovirus type 2 and Mycoplasma hyopneumoniae genetically engineered vaccine. In this article, we used prokaryotic expression to express and purify recombinant PorB protein, four different concentrations of PorB protein, Freund's adjuvant with two genetically engineered vaccines were combined with subcutaneous immunization of mice. Our study shows that the appropriate dose of the recombinant protein PorB can enhance the levels of humoral and cellular responses induced by two genetically engineered vaccines in a short period of time in mice. The PorB adjuvant group may cause statistically higher antibody titers for both genetically engineered vaccines compared to Freund's commercial adjuvant (P<0.001). The recombinant protein PorB may be a good candidate adjuvant for improving the protective effect of vaccines against porcine circovirus type 2 and Mycoplasma hyopneumoniae, and the protein can be used for future practical applications.
oligonucleotides
2023-01-16 | Tracing the Negative Results of Multiplex Real-Time PCR Assay for Diagnosis of Bacterial Pediatrics Meningitis
The death because of meningitis remains high in some parts of the world. It is important to know the specific cause of meningitis because the treatment differs depending on the cause. This study aimed to trace the false-negative results of multiplex RT-PCR to detect Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis serogroup by two different molecular methods. In this study, the CSF of the suspicious pediatric for acute bacterial meningitis among children aged 1 month to 14 years who are admitted to the hospitals in four cities of a certain region of Iran was collected. S. pneumoniae, H. influenzae, and N. meningitidis in CSF samples were detected by single-tube multiplex RT-PCR and specific RT-PCR with a probe on the same specimens. In this cross-sectional study, 506 CSF samples were collected during one year. The multiplex RT-PCR can detect 3.3% and 2.2% of S. pneumoniae and H. influenzae, respectively. N. meningitidis was not detected. The CSF analysis was abnormal in 53% of 506 patients. On the other hand, 11.5%, 4.8%, and 4.1% of S. pneumoniae, H. influenzae, and N. meningitidis were identified, respectively, by specific RT-PCR assay, exactly on the same specimens. Various types of PCR can be used for pathogen identification. As we change the type of PCR in our study, we could approximately increase 15% our positive results and also consequently decrease our false-negative responses.
2021-04-07 | Quality of metagenomic DNA extracted for molecular identification of microorganisms from CSF samples of patients with suspected cerebrospinal meningitis in northern Nigeria
Background: Following an increase in the practice of starting antimicrobial therapy prior to clinical sample collection, the ability to confirm pathogenic microorganisms of bacterial meningitis has decreased by approximately 30%. Culture results may be false negative when fastidious or culture-resistant bacteria are involved or when patient samples are obtained after antimicrobial therapy has started. Molecular diagnosis using PCR can be performed directly on clinical samples after metagenomic DNA (mDNA) extraction not requiring live organisms for a positive result. The specific objectives of this study are to perform mDNA extraction directly from cerebrospinal fluids (CSF) using appropriate spin column method, and to determine the quality of the mDNA elute.Methodology: Cerebrospinal fluid specimens were collected from 210 patients with suspected acute cerebrospinal meningitis (CSM) in the Federal Capital Territory and some States in Northern Nigeria during the 2017 and 2018 outbreak seasons. Metagenomic DNA was extracted from approximately 200µL of CSF specimens using the Qiagen QIAamp(R) DNA Mini kit specific for bacterial agents only. DNA quality check was performed on all DNA elutes using fluorometric, spectrophotometric and agarose gel electrophoresis methods.Results: Of the 210 CSF samples analyzed microbiologically, Gram reaction was positive in 94 cases (44.8 %) but only 17 (8.1 %) were culture positive for two of the three major bacterial causes of meningitis. One hundred and eighty (85.7%) samples had DNA concentrations ≥ 0.005 ng/µL, 55 (30.6 %) of these had DNA purity (A260/A280) of ≥ 1.7, 103 (57.2%) had purity value between 1.0 - 1.69, 14 (7.8%) had value of 0.57 - 0.99, and 8 (4.4%) failed purity evaluation with value of 0.00 at A260/A280.Conclusion: The essence of mDNA extraction is multipurpose. A multiplex PCR can be performed on the extracted mDNA to interrogate the presence of microbial pathogens of interest using specific primers and probes (when applicable). Quality mDNA from CSF samples will ensure successful qPCR results for rapid and accurate detection of bacterial pathogens in meningitis. This will eliminate the challenges associated with traditional culture methods. Keywords: Meningitis, CSF, DNA Quality Check, Fluorometry
2020-09-17 | A homopolymeric adenosine tract in the promoter region of nspA influences factor H-mediated serum resistance in Neisseria meningitidis.
Although usually asymptomatically colonizing the human nasopharynx, the Gram-negative bacterium Neisseria meningitidis (meningococcus) can spread to the blood stream and cause invasive disease. For survival in blood, N. meningitidis evades the complement system by expression of a polysaccharide capsule and surface proteins sequestering the complement regulator factor H (fH). Meningococcal strains belonging to the sequence type (ST-) 41/44 clonal complex (cc41/44) cause a major proportion of serogroup B meningococcal disease worldwide, but they are also common in asymptomatic carriers. Proteome analysis comparing cc41/44 isolates from invasive disease versus carriage revealed differential expression levels of the outer membrane protein NspA, which binds fH. Deletion of nspA reduced serum resistance and NspA expression correlated with fH sequestration. Expression levels of NspA depended on the length of a homopolymeric tract in the nspA promoter: A 5-adenosine tract dictated low NspA expression, whereas a 6-adenosine motif guided high NspA expression. Screening German cc41/44 strain collections revealed the 6-adenosine motif in 39% of disease isolates, but only in 3.4% of carriage isolates. Thus, high NspA expression is associated with disease, but not strictly required. The 6-adenosine nspA promoter is most common to the cc41/44, but is also found in other hypervirulent clonal complexes.
2014-05-27 | Lipopolysaccharide engineering in Neisseria meningitidis: structural analysis of different pentaacyl lipid A mutants and comparison of their modified agonist properties.
Engineering the lipopolysaccharide (LPS) biosynthetic pathway offers the potential to obtain modified derivatives with optimized adjuvant properties. Neisseria meningitidis strain H44/76 was modified by expression of the pagL gene encoding lipid A 3-O-deacylase from Bordetella bronchiseptica and by inactivation of the lgtB gene encoding the terminal oligosaccharide galactosyltransferase. Mass spectrometry analysis of purified mutant LPS was used for detailed compositional analysis of all present molecular species. This determined that the modified LPS was mainly pentaacylated, demonstrating high efficiency of conversion from the hexaacyl to the 3-O-deacylated form by heterologous lipid A 3-O-deacylase (PagL) expression. MS analyses also provided evidence for expression of only one major oligosaccharide glycoform, which lacked the terminal galactose residue as expected from inactivation of the lgtB gene. The immunomodulatory properties of PagL-deacylated LPS were compared with another pentaacyl form obtained from an lpxL1(-) mutant, which lacks the 2' secondary acyl chain. Although both LPS mutants displayed impaired capacity to induce production of the pro-inflammatory cytokine IL-6 in the monocytic cell line Mono Mac 6, induction of the Toll-interleukin-1 receptor domain-containing adaptor-inducing interferon-β-dependent chemokine interferon-γ-induced protein 10 was largely retained only for the lgtB(-)/pagL(+) mutant. Removal of remaining hexaacyl species exclusively present in lgtB(-)/pagL(+) LPS demonstrated that these minor species potentiate but do not determine the activity of this LPS. These results are the first to indicate a qualitatively different response of human innate cells to pentaacyl lpxL1(-) and pagL(+) LPS and show the importance of detailed structure-function analysis when working with modified lipid A structures. The pagL(+) LPS has significant potential as immune modulator in humans.
2003-09-18 | Induction of a protective capsular polysaccharide antibody response to a multiepitope DNA vaccine encoding a peptide mimic of meningococcal serogroup C capsular polysaccharide
Summary Systemic infection by encapsulated organisms, such as Neisseria meningitidis , is a major cause of morbidity and mortality worldwide, especially in individuals less than 2 years of age. Antibodies directed at the capsular polysaccharide are shown to be protective against disease by inducing complement‐dependent bactericidal activity. The current polysaccharide vaccine has been shown to be poorly immunogenic in high‐risk groups and this is probably related to its T‐independent properties. An alternative approach to eliciting a T‐dependent serum immunoglobulin G (IgG) antibody response to encapsulated pathogens is DNA vaccination. We assessed the immunogenicity of a multiepitope DNA vaccine encoding a T‐cell helper epitope and a peptide mimic of N. meningitidis serogroup C. The DNA construct induced a significant anti‐polysaccharide antibody response that was bactericidal. Mice immunized with the DNA construct were subsequently protected against challenge with a lethal dose of N. meningitidis serogroup C.
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Drug Discovery Landscape
2 orphan drug designations for Meningococcal meningitis.
2 orphan drug designations for Meningococcal meningitis.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Opebacan [Neuprex] | proteins | EMA | — | [INACTIVE] XOMA Ireland Limited |
Recombinant bactericidal/permeability-increasing protein | proteins | FDA | — | Xoma (US) LLC |
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