Meningitis : An Inflammation Of The Meninges

Abstract

Meningitis, an inflammation of the meninges surrounding the brain and spinal cord, continues to pose major global health challenges owing to its high morbidity and mortality, and frequent long-term neurological sequelae. This article reviews recent advances in epidemiology, etiology, pathophysiology, diagnosis, treatment, prevention, and research directions, drawing on the latest WHO guidelines (2025) and publications through 2024–2025. Bacterial meningitis, particularly due to Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, and Mycobacterium tuberculosis, remains the most severe form. Recent outbreaks (e.g. in Nigeria, Iraq) highlight gaps in surveillance, vaccine coverage, and healthcare infrastructure. New WHO guidelines (2025) aim to standardize diagnosis and treatment, particularly in low- and middle-income countries. Innovations in adjunctive therapies, diagnostics (e.g. radiomics, point-of-care), and novel vaccine formulations, along with global initiatives (e.g. “Defeating Meningitis by 2030”), provide optimism. However, barriers remain: delays in presentation, antibiotic resistance, inadequate follow-up care for disabling outcomes, and unequal access to vaccines. The article concludes with priority areas for research and policy to reduce the burden of meningitis globally.

Introduction

Meningitis refers to inflammation of the leptomeninges (arachnoid and pia mater) and the cerebrospinal fluid (CSF) spaces. It may be caused by infectious agents (bacteria, viruses, fungi, parasites) or non-infectious causes (autoimmune disease, malignancy, certain drugs). It is a medical emergency: in bacterial meningitis particularly, death or significant disability can occur within 24-48 hours after symptom onset if treatment is delayed. The high stakes make early recognition, rapid diagnosis, and prompt treatment essential.

Despite advances in vaccination, antibiotic therapy, and supportive care, meningitis remains a global public health problem. Recent WHO estimates indicate that bacterial meningitis causes high mortality (≈ one in six cases) and frequent severe sequelae among survivors. Epidemiological patterns differ by geography, age-group, socioeconomic status, and the availability of healthcare resources and vaccines. The aim of this article is to synthesize the latest research (up to 2025) on meningitis: its causes, global burden, pathophysiology, clinical features, current diagnostic and therapeutic strategies, prevention and control, and promising new advances, along with challenges remaining.

Etiology and Classification

Infectious vs Non-infectious

Infectious meningitis is far more common and clinically urgent. Within this category:
- Bacterial meningitis is the most severe, with rapid progression and high risk of death and permanent damage.
- Viral meningitis (often called aseptic meningitis) tends to be milder, though some viral agents (e.g. herpesviruses, enteroviruses) can also cause serious disease.
- Fungal, parasitic, and mycobacterial causes are less frequent but important, especially in immunocompromised or endemic settings (e.g. Cryptococcus, Histoplasma, Acanthamoeba, Mycobacterium tuberculosis).
Non-infectious causes include malignancy, autoimmune disease, certain medications, trauma, and chemical/sterile inflammation.

Major Bacterial Pathogens

According to WHO (2025), main agents of acute bacterial meningitis globally are:

Neisseria meningitidis (“meningococcus”) – multiple serogroups (A, B, C, W, X, Y) that cause epidemics especially in the “meningitis belt” of sub-Saharan Africa.
Streptococcus pneumoniae (pneumococcus) – significant in children, adults; often severe.
Haemophilus influenzae type b (Hib) – once a leading cause in young children; vaccine use has reduced incidence in many places, though residual disease persists.
Streptococcus agalactiae (Group B Streptococcus) – particularly in neonates.
Mycobacterium tuberculosis – in endemic areas (causing tuberculous meningitis, which has different features and course).

Classification by Time Course and Setting

Acute meningitis: rapid onset (hours to days) — typically bacterial, some viral.
Subacute or chronic meningitis: slower onset (weeks) — includes TBM, fungal, certain atypical organisms.
Epidemic vs sporadic: Certain bacterial types (especially N. meningitidis) tend to produce epidemics in certain geographies or under conditions of crowding.

Age-based Classification

Neonatal meningitis (first 28 days)
Infants and children (1 month to ~5 years)
Adolescents and young adults
Adults
Immunocompromised or elderly populations

Different pathogens dominate in different age groups.

Pathophysiology

Understanding how meningitis develops is key both to prevention and to treatment.

Entry of pathogen
Pathogens may gain access to the central nervous system (CNS) via hematogenous spread (after colonizing nasopharynx or other sites), by direct extension (e.g. from otitis media, mastoiditis, skull fracture), or via neural routes in some viral/fungal pathogens.
Crossing the blood-brain barrier (BBB) / blood–CSF barrier
Some pathogens (e.g. Neisseria meningitidis) can adhere to endothelial cells, resist complement, and cross via transcellular or paracellular pathways. Others may be carried within immune cells or via breakdown of the barrier due to inflammation.
Inflammatory response
Once in the subarachnoid space, pathogen proliferation and the host immune response (neutrophils, macrophages, release of cytokines such as TNF-α, IL-1β, IL-6) lead to increased vascular permeability, influx of leukocytes, release of reactive oxygen species, proteases. This causes:
- Cerebral edema (both cytotoxic and vasogenic)
- Increased intracranial pressure
- Impaired CSF flow and sometimes hydrocephalus
- Vasculitis of meningeal vessels; possible thrombosis leading to infarction.
Neuronal injury
Hypoxia due to reduced perfusion, oxidative stress, excitotoxicity, and direct toxicity of bacterial products (e.g. pneumococcal cell wall components) contribute to neuronal damage. Damaged neurons plus secondary factors (seizures, raised intracranial pressure) lead to permanent deficits if not reversed promptly.
Systemic effects
Particularly in bacterial meningitis, sepsis may accompany, causing multi-organ dysfunction. Also, systemic inflammatory response may worsen vascular issues (coagulopathy, DIC) and contribute to poor perfusion including of the brain.
Recovery and sequelae
Even when pathogen is cleared, residual effects may persist: hearing loss, cognitive impairment, motor deficits, seizures, psychological effects. In tuberculous meningitis, additional mechanisms include granulomatous inflammation, fibrotic exudates at base of brain obstructing CSF, vasculitic infarcts.

Epidemiology

Global Burden

WHO estimates that bacterial meningitis caused approximately 1.6 million cases in 2019, with about 240,000 deaths.
Around one in six people who get bacterial meningitis die; among survivors, one in five (≈ 20%) have severe complications.

Geographic Distribution

The African Meningitis Belt, stretching from Senegal to Ethiopia, is the region with the highest risk for repeated meningococcal meningitis epidemics. Risk factors include hot, dry seasons, crowding, low immunity.
Low- and middle-income countries (LMICs) carry disproportionate burden in terms of incidence, mortality, and sequelae, often due to delayed diagnosis, limited access to treatment, and lower vaccination coverage.

Recent Outbreaks and Trends

Nigeria between October 2022 and April 2023: ~1,686 suspected cases, 124 deaths, CFR ~7% in multiple states.
Iraq, 2023: outbreak among children in Halabja Governorate; ~200 suspected meningitis cases, with both viral and bacterial etiologies studied.
United States: increase in meningococcal disease in 2022-2023, with serogroup Y driving much of recent rise; in the U.S., case numbers in 2023 exceeded pre-COVID levels.

Risk Factors

Age (neonates, young children, elderly)
Immunodeficiency (HIV, immunosuppressive therapy)
Crowded living conditions (refugee camps, military barracks, dormitories)
Poor vaccination coverage
Seasonal/climatic factors in endemic regions
Travel and migration from high-incidence regions

Clinical Features

The presentation of meningitis depends on age, causative organism, and speed of onset. Some general features and age‐specific considerations are:

Common Signs and Symptoms

Fever
Headache (often severe)
Neck stiffness (nuchal rigidity)
Photophobia (light sensitivity)
Vomiting
Altered level of consciousness or confusion
In severe bacterial meningitis, rash (in meningococcal disease), seizures

Age-Specific Features

Neonates: irritability, poor feeding, hypothermia or fever, bulging fontanelle, apnea, lethargy.
Infants and young children: possibly non-specific signs, vomiting, seizures, irritability, maybe less pronounced nuchal rigidity.
Older children and adults: more classical triad of fever, neck stiffness, headache; may have photophobia, confusion.

Tuberculous Meningitis

Slower onset over days to weeks
Prodromal constitutional symptoms: weight loss, night sweats, malaise
Cranial nerve involvement
Hydrocephalus signs, raised intracranial pressure (ICP), and possible infarctions

Complications

Hearing loss (sensorineural)
Seizures, focal neurological deficits
Cognitive impairment, learning disabilities
Hydrocephalus
Brain abscess in some cases
Mortality: Even with treatment, significant death rates especially in LMICs

Diagnosis

Accurate and prompt diagnosis is essential, since early treatment greatly influences outcome.

Clinical Assessment

Recognition of signs and symptoms
Assessment of risk factors and epidemiological context

Laboratory and Imaging Investigations

Lumbar Puncture (LP) and Cerebrospinal Fluid (CSF) analysis
- Opening pressure measurement
- CSF appearance (cloudy, purulent vs clear)
- Cell count & differential (neutrophils vs lymphocytes)
- Glucose (often low in bacterial, TB, fungal), protein (elevated)
- Gram stain, culture (bacterial)
- PCR or molecular testing to detect viral/fungal/TB pathogens
- Antigen detection (latex agglutination)
Blood tests
- Blood cultures
- Complete blood count, inflammatory markers (CRP, ESR)
- Merits of using serum procalcitonin
Imaging
- CT / MRI to rule out mass lesions, raised ICP before LP if suspicion is high
- In TBM, MRI may show basal meningeal enhancement, hydrocephalus, infarcts
Other modalities
- Radiomics and novel imaging classifiers: e.g. recent work classifying tuberculous meningitis using MRI features in graph-based models to distinguish from other processes.
- Point-of-care diagnostics: rapid antigen tests, multiplex PCR panels

WHO 2025 Guidelines

The WHO published its first global guidelines on meningitis diagnosis, treatment and care in April 2025. Key recommendations include:

Speeding up detection: improve diagnostic capacity at first and second level health facilities
Empirical antibiotic therapy to be started early, even prior to full confirmation, in high suspicion cases
Use of adjunctive treatments and supportive care, including management of raised intracranial pressure and preventing secondary brain injury
Specific guidance by age group, and differentiating epidemic vs non-epidemic settings

Management and Treatment

General Principles

Early empirical therapy is essential. Delays in treatment increase risk of death and sequelae.
Selection of antibiotic should cover likely pathogens, and be adjusted once organism and sensitivity known.

Empirical Antibiotic Therapy

Neonates: broad spectrum agents covering Group B Streptococcus, E. coli, Listeria (where prevalent)
Children and adults: cover N. meningitidis, S. pneumoniae, H. influenzae; empirical regimens often include third-generation cephalosporin (e.g. ceftriaxone or cefotaxime) ± vancomycin, depending on local resistance patterns.
In settings with TB endemicity and suspicion of TBM, include anti-TB therapy after diagnostic confirmation or strong suspicion.

Adjunctive therapies

Corticosteroids (e.g. dexamethasone) in certain bacterial meningitis (especially S. pneumoniae) to reduce inflammatory damage in subarachnoid space; best if given before or with first dose of antibiotics.
Supportive care: managing intracranial pressure, seizures, fluid balance, electrolyte correction
In animal models: systematic review (2024) of adjunctive treatments for pneumococcal meningitis showed some promising options (anti-inflammatory agents, neuroprotective agents) for reducing hearing loss, cognitive impairment. However, most remain in preclinical stage.

Special Management: Tuberculous Meningitis

Anti-tuberculous therapy (multiple drugs over extended duration, often ≥9 to 12 months)
Adjunctive corticosteroids reduce mortality and neurological sequelae

Epidemic settings

Mass vaccination campaigns when appropriate serogroups are involved
Rapid case identification and treatment, sometimes with community outreach

Prevention and Control

Vaccines

Vaccination has dramatically reduced incidence of certain bacterial causes (e.g. Hib, some N. meningitidis, S. pneumoniae) in many parts of the world.
New vaccine developments: In Nigeria, the rollout of Men5CV vaccine, which protects against five major meningococcal serogroups, was initiated, marking progress in epidemic prevention.
Vaccines for S. pneumoniae (conjugate vaccines), H. influenzae type b, and meningococcal conjugate vaccines (A, C, W, Y, B etc.) are central parts of prevention strategies.

Surveillance, Outbreak Preparedness

Strengthening disease surveillance systems to detect outbreaks early
Health systems prepared to respond with vaccine stockpiles, laboratory capacity
WHO’s global roadmap “Defeating Meningitis by 2030” emphasizes: eliminating bacterial meningitis epidemics; reducing vaccine-preventable meningitis cases by 50%; reducing deaths by 70%; decreasing disability and improving quality of life for survivors.

Public Health Measures

Awareness campaigns to improve recognition of symptoms and earlier presentation to healthcare
Ensuring vaccine coverage, cold chain integrity, access in remote/rural areas
Infection control measures in hospitals, especially for neonatal and nosocomial meningitis

Prognosis

Mortality remains high for bacterial meningitis: globally, approximately 1 in 6 people die of bacterial meningitis.
Among survivors, up to 20–25% may have severe sequelae (hearing loss, neurological deficits, cognitive impairment).
Prognosis is improved when: diagnosis is rapid; empirical therapy is initiated early; appropriate adjunctive measures are taken; healthcare system with good ICU support is available.
Prognosis for tuberculous or fungal meningitis is generally worse, given delayed diagnosis and treatment, and higher risk of irreversible damage.

Recent Advances & Research Directions

WHO Global Guidelines (2025)
The release of these guidelines brings standardized evidence-based recommendations for diagnosis, treatment, and long-term care globally, especially important for uniformity in LMICs.
Adjunctive Therapies
Animal model studies (e.g. for pneumococcal meningitis) are identifying neuroprotective agents and anti-inflammatories that may reduce long-term sequelae. Translating these into human clinical trials is a key next step.
Diagnostics and Imaging
Novel approaches like radiomics and graph classification of MRI in tuberculous meningitis to support non-invasive diagnosis or differentiation.
Vaccine Development
Formulations that cover more serogroups (e.g. Men5CV), improved conjugate vaccines, potentially more affordable vaccines for use in LMICs.
Epidemiological modelling and behaviour
Studies modeling carriers, vaccination behavior, spread thresholds to predict epidemic risk and guide public health interventions.
Global Initiatives
“Defeating Meningitis by 2030” roadmap aiming at ambitious reductions in cases, deaths and disability.
Health System Strengthening
Improved access to diagnosis and treatment, reducing delays, expanding capacity (especially in rural and resource-limited settings), long-term care for post-meningitis disabilities.

Challenges and Gaps

Delayed presentation: many patients in LMICs reach health facilities late, reducing the window for effective treatment.
Limited diagnostic capacity: lack of laboratories, access to advanced imaging, molecular diagnostics in many settings.
Antibiotic resistance: emerging resistance in bacterial pathogens complicates empirical treatment and increases treatment failure risk.
Vaccine coverage gaps: vaccine hesitancy, cost, logistical and cold-chain issues impede full reach; serogroup shifts can undermine vaccine effectiveness.
Post-disease care: In many settings, care for sequelae (hearing aids, rehabilitation, educational support) is inadequate, so survivors with disabilities suffer in the long term.
Resource constraints: finances, infrastructure, trained healthcare personnel especially in rural or impoverished regions.

Future Research Priorities

Clinical trials of adjunctive therapies to validate what is promising in animal models (neuroprotection, anti-inflammation beyond steroids, antioxidant therapies).
Rapid diagnostics suitable for point-of-care, especially tools that can distinguish bacterial vs viral vs TB vs fungal causes quickly.
Genomic surveillance of bacterial strains and serogroups to monitor vaccine escape, emergence of new virulent clones, and antibiotic resistance.
Improved vaccines: broader serogroup coverage, longer duration of immunity, thermostable vaccines, low cost.
Implementation research: finding best ways to strengthen health systems, improve vaccine uptake, reduce diagnostic and treatment delays in low-resource settings.
Rehabilitation and care for survivors: neurological, cognitive, auditory rehabilitation; psychosocial support; assessment of quality of life.

Conclusion

Meningitis remains a serious global health threat despite advances in our understanding, vaccines, and treatments. While bacterial meningitis continues to be the leading cause of death and disability, significant strides are being made: globally adopted guidelines (WHO 2025), vaccine innovations (e.g. Men5CV), better diagnostic tools, and research into adjunctive therapies. To achieve the ambitious targets of halving vaccine-preventable meningitis cases, reducing deaths by 70%, eliminating epidemics, and improving life quality for survivors (as per WHO’s “Defeating Meningitis by 2030” roadmap), concerted action is needed:

Ensuring access to effective vaccines globally
Enhancing diagnostic capacity and treatment services, particularly in LMICs
Encouraging earlier presentation and recognition of cases
Investing in research to translate promising adjunctive therapies into human benefit
Strengthening post-infection care to address long-term sequelae

If these are realized, the global burden of meningitis can be substantially reduced in the coming decade.

References

WHO. (2025, April 1). Meningitis fact sheet. World Health Organization.
WHO. (2025, April 10). WHO launches first-ever guidelines on meningitis diagnosis, treatment and care.
WHO. (2023). Disease outbreak news: Meningitis - Nigeria.
WHO. (2023). Epidemiology and aetiology of the 2023 meningitis outbreak among children in Iraq.
Centers for Disease Control and Prevention (CDC). Meningococcal Disease Surveillance and Trends; U.S. data, 2023.
Systematic review of adjunctive treatments for pneumococcal meningitis in animal models (2024).
Agarwal, S., V H, G., Sinha, N., Indoria, A., Netravathi, M., & Saini, J. (2025). Graph Classification and Radiomics Signature for Identification of Tuberculous Meningitis. arXiv.
Yaga, S. J., & Saporu, F. W. O. (2023). A study of a deterministic model for meningitis epidemic. arXiv.