Meningitis is an infection of the meninges, the protective membranes covering the brain and spinal cord. It is a serious condition that can lead to significant morbidity and mortality, particularly in the pediatric population. Although bacterial meningitis is the most dangerous form, viral, fungal, and parasitic infections can also lead to meningitis. In the era of vaccination, the incidence of some types of meningitis has decreased significantly, but the condition remains a major cause of neurological impairment and death in children worldwide.
This article provides an in-depth review of the epidemiology, pathogenesis, pathophysiology, differential diagnoses, clinical features, diagnosis, treatment, and potential complications of meningitis in pediatric patients.
Epidemiology
Meningitis in children is most commonly caused by viral or bacterial infections. The incidence of bacterial meningitis has decreased significantly in many parts of the world due to vaccination, particularly with vaccines targeting Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b (Hib). However, bacterial meningitis remains a major concern, especially in neonates and infants.
- Bacterial meningitis: The overall incidence of bacterial meningitis in the United States is approximately 0.5–1 case per 100,000 children per year. It is more common in infants under 2 months of age due to immaturity of the immune system. Invasive meningococcal disease, caused by Neisseria meningitidis, has an incidence of 0.1–1 case per 100,000 in the general population, but the incidence is higher in adolescents.
- Viral meningitis: The incidence of viral meningitis is more difficult to quantify, as it is less likely to be reported and may not always be diagnosed. Enteroviruses are the most common cause of viral meningitis, especially in the summer and fall months.
- Fungal meningitis: Fungal infections such as cryptococcal meningitis are rare but can occur in immunocompromised children including those with HIV or on immunosuppressive therapy.
- Parasitic meningitis: This is very rare and is typically seen in children exposed to specific environmental factors or immunocompromised states.
Several factors increase the risk of meningitis in children:
- Age: Infants, especially those under 2 months of age, are at the highest risk due to an immature immune system.
- Vaccination status: Lack of vaccination or incomplete vaccination against Hib, pneumococcus, and meningococcus increases susceptibility to bacterial meningitis.
- Immunocompromised states: Conditions such as HIV, cancer, and the use of immunosuppressive medications (e.g., steroids, chemotherapy) predispose children to infections, including meningitis.
- Close living conditions: Children living in close quarters, such as in dormitories, military barracks, or group homes, are at increased risk of meningococcal meningitis.
- Underlying medical conditions: Conditions like sickle cell disease, splenectomy, and chronic lung disease can increase the risk of infection as they are often associated with decreased immune system rigor.
Pathogenesis and pathophysiology
Meningitis occurs when pathogens invade the central nervous system (CNS), typically through the bloodstream or direct extension from adjacent structures such as the ears or sinuses. The invasion of the meninges triggers an inflammatory response, which can cause significant neurological damage. Common infections that can progress to meningitis include otitis media and sinusitis, while direct contact of the spinal fluid with the outside world also increase the risk of infection (such as penetrating head trauma or neurosurgery).
Bacterial meningitis
- Streptococcus pneumoniae: The most common cause of bacterial meningitis in children older than 2 months of age, particularly in unvaccinated children.
- Neisseria meningitidis: A leading cause of meningitis in adolescents and young adults, it can lead to meningococcal septicemia. These patients are at high risk for DIC and can develop adrenal failure due to hemorrhaging of the adrenal glands (Waterhouse-Friderichsen syndrome).
- Haemophilus influenzae type b (Hib): Though less common since the introduction of the Hib vaccine, it remains an important pathogen in infants and young children. Non-typeable H flu is not covered by the Hib vaccines and thus is also a culprit in both the vaccinated and unvaccinated populations.
- Group B Streptococcus (GBS): The most common cause of bacterial meningitis in neonates, often acquired during delivery.
- Escherichia coli: Also a common cause of neonatal bacterial meningitis, especially in premature infants.
- Listeria monocytogenes: An important cause of meningitis in neonates, older adults, and immunocompromised patients. Although this is less common than in past years, the increase in listeria outbreaks in the United States food supply could lead to an uptick.
- Bacteremia: The organism enters the bloodstream, after which it can then cross the blood-brain barrier into the spinal fluid.
- Invasion of the meninges: The bacteria bind to endothelial cells, initiating an inflammatory cascade.
- Inflammation: Pro-inflammatory cytokines, including tumor necrosis factor (TNF) and interleukins, are released, leading to endothelial dysfunction, edema, and increased intracranial pressure (ICP).
- Cerebral injury: The inflammation can cause neuronal injury (seizures), cerebral edema (increased ICP), and hydrocephalus.
organisms by age group
Bacterial meningitis is caused by different organisms depending on the age of the child, with the causative pathogens shifting as the immune system matures and as vaccination programs change the landscape of infectious diseases. Below is an overview of the key pathogens causing bacterial meningitis in infants, children, and adolescents.
In neonates, the most common pathogens are those typically acquired during delivery, as well as those affecting the neonatal immune system.
- Group B Streptococcus (GBS): The leading cause of neonatal bacterial meningitis, accounting for 30–40% of cases in this age group. GBS may be transmitted during vaginal delivery, but exposures may also occur weeks after delivery.
- Escherichia coli: Particularly prevalent in premature or low birth weight infants, this pathogen is a significant cause of neonatal meningitis. K1 strain is associated with a higher incidence of meningitis.
- Listeria monocytogenes: An important pathogen in neonates, especially in those with in utero exposure. Infection can occur from contaminated food or vertical transmission from the mother during pregnancy.
- Streptococcus pneumoniae: Less common in neonates than in older infants or children, but it can occur in this age group, particularly in cases of preterm birth or chronic medical conditions.
In infants, bacterial meningitis pathogens shift slightly as the child’s immune system develops and maternal immunity wanes.
- Streptococcus pneumoniae: The most common cause of bacterial meningitis in infants after the neonatal period, particularly in those between 1–12 months. Pneumococcal meningitis is associated with high morbidity and mortality.
- Neisseria meningitidis: This pathogen begins to emerge as a cause of meningitis after the first few months of life. It typically presents in a more acute form, often associated with meningococcemia, a systemic form of the infection.
- Haemophilus influenzae type b (Hib): Once a leading cause of pediatric bacterial meningitis, the incidence has dramatically decreased in regions with widespread Hib vaccination. However, it remains an important pathogen in non-vaccinated children, particularly in infants.
- Group B streptococcus: Particularly in infants younger than 3 months, GBS is a significant pathogen.
In children beyond the first year, the spectrum of bacterial pathogens broadens, with an increasing role of Neisseria meningitidis and Streptococcus pneumoniae.
- Streptococcus pneumoniae: Remains the most common cause of bacterial meningitis in children, especially in those aged 1–10 years, despite the availability of the pneumococcal vaccine. Pneumococcal meningitis can present with severe symptoms, including high fever, seizures, and neurologic deficits.
- Neisseria meningitidis: A leading cause of bacterial meningitis in children, especially in school-aged children. Meningococcal meningitis is more common in children older than 2 years and often presents with a rapidly progressive course and potential for meningococcemia.
- Haemophilus influenzae type b (Hib): Still a pathogen in children who have not received the Hib vaccine, but the incidence has significantly decreased with vaccination programs. In non-vaccinated populations, Hib remains a key cause of meningitis in young children.
In adolescents, Neisseria meningitidis becomes the dominant pathogen, though Streptococcus pneumoniae is also important, especially in those with underlying medical conditions or incomplete vaccination.
- Neisseria meningitidis: This is the most common cause of bacterial meningitis in adolescents, particularly in teenagers and young adults. Meningococcal disease is often associated with outbreaks in college dormitories, military barracks, or boarding schools due to close living conditions. Meningococcal meningitis can present with rapid onset and associated septicemia.
- Streptococcus pneumoniae: A significant pathogen in adolescents as well, though the incidence in this age group has decreased with the use of the pneumococcal conjugate vaccine.
This age-based pattern of bacterial pathogens emphasizes the importance of vaccination programs, especially against pneumococcus, meningococcus, and Hib, as well as the need for empirical treatment to cover the broad spectrum of potential pathogens when bacterial meningitis is suspected in a pediatric patient.
| Age group | Most common pathogens |
| Neonates (0–28 days) |
|
| Infants (1–12 months) |
|
| Children (1–10 years) |
|
| Adolescents (11–18 years) |
|
Viral meningitis/encephalitis
Viral infections can cause both meningitis and encephalitis (inflammation of the brain tissue itself). Common culprits include enteroviruses, herpes simplex virus (HSV), varicella-zoster virus (VZV), although any virus can be implicated. Viral meningitis/encephalitis typically has a milder course than bacterial meningitis and is often self-limited, though some cases may cause long-term complications. However, it is difficult to differentiate viral and bacterial etiologies clinically, thus these patients still receive a rigorous work up and treatment.
Differential diagnosis
Several conditions can mimic the clinical features of meningitis, making an accurate differential diagnosis essential:
- Encephalitis: Inflammation of the brain itself, often caused by viral infections or autoimmune responses, can present with fever, altered mental status, and neurological deficits.
- Abscesses: Brain abscesses can present with fever, headache, and focal neurological signs, and can sometimes lead to meningeal irritation.
- Septicemia: In infants, bacteremia can cause fever, irritability, and poor feeding, which can mimic meningitis.
- Tuberculous meningitis: Although rare in the developed world, tuberculosis can cause a subacute form of meningitis with a gradual onset and systemic symptoms.
- Cerebral malaria: In endemic regions, cerebral malaria caused by Plasmodium falciparum can present similarly, particularly with fever, altered consciousness, and seizures.
- Subarachnoid hemorrhage: Can present with a similar acute onset of headache, photophobia, and vomiting, but lacks fever and infectious signs.
- Systemic lupus erythematosus (SLE): Lupus can cause aseptic meningitis as part of a broader autoimmune picture.
Clinical features
Meningitis in children presents with a range of nonspecific and specific features, and the clinical course can vary depending on the etiology and age of the patient.
- Fever and malaise: A hallmark of meningitis, often with rapid onset.
- Headache: Common, particularly in older children, and often severe.
- Photophobia: Sensitivity to light.
- Nausea/Vomiting: Can be due to systemic inflammation, but in severe cases due to increased intracranial pressure.
- Neck stiffness: A classic sign but may be difficult to assess in infants.
- Bulging fontanelle: Can be seen in any child with an open fontanelle, reflective of the increased intracranial pressure that comes with the inflammation.
- Altered mental status: This may include irritability, lethargy, confusion, or seizures. In severe cases, coma may ensue.
- Seizures: Seen in severe cases.
- Kernig sign: inability to extend the lower leg when the hip is flexed to 90 degrees, reflective of inflammation of the sciatic nerve roots that occurs with meningeal inflammation. Not as common in viral meningitis.
- Brudzinski sign: When the patient is laying supine, neck flexion results in involuntary flexion of the hips and knees due to stretching of the inflamed nerve roots. Not as common in viral meningitis.
- Poor feeding, vomiting.
- Hypotonia or hypertonia.
- Irritability or lethargy.
- Bulging fontanelle (due to increased intracranial pressure).
- Seizures may be the first sign of meningitis in infants.
Diagnosis
The diagnosis of meningitis is based on a combination of clinical features, laboratory tests, and imaging studies.
- Bacterial meningitis is a medical emergency and requires immediate treatment.
- Diagnostic and treatment steps should be initiated simultaneously, and empiric treatment should not be delayed for diagnostic steps.
- If the patient is stable and has no LP contraindications: Perform LP as soon as possible before starting empiric antibiotics.
- If the patient is unstable, requires neuroimaging, or has relative contraindications to LP (e.g., coagulopathy): Defer LP and start empiric antibiotic treatment.
The gold standard for diagnosing meningitis is lumbar puncture (LP), which allows for the analysis of cerebrospinal fluid (CSF). The following findings are suggestive of different types of meningitis:
- Bacterial meningitis:
- Cloudy or purulent CSF.
- Elevated white blood cell count (pleocytosis based on norms for age), predominantly neutrophils (>50%).
- Low glucose (<40% of serum glucose).
- High protein (>100mg/dL).
- Elevated opening pressure (>25cm H20).
- Positive gram stain.
- Viral meningitis:
- Clear or slightly cloudy CSF.
- Slightly elevated white blood cell count, predominantly lymphocytes.
- Normal or mildly decreased glucose (40–80mg/dL).
- Normal or mildly elevated protein (20–80mg/dL).
- Negative gram stain.
- Fungal or TB meningitis: May show markedly increased protein and a mixed pleocytosis with predominantly lymphocytes.
- Aseptic meningitis (due to medications) can have a slightly elevated white blood cell count but normal protein and glucose.
Blood cultures should be obtained before antibiotic administration in all suspected cases of bacterial meningitis to help identify the causative pathogen.
- Brain imaging (non-contrast CT scan) is generally performed before lumbar puncture in children with altered mental status, focal neurological findings, papilledema, or concerns for increased intracranial pressure. Imaging can help identify structural abnormalities, abscesses, or evidence of raised intracranial pressure.
- Correction of significant coagulopathy is important prior to attempting lumbar puncture. This may include vitamin K to address elevated INR or platelet transfusion.
- Patients may require ultrasound guided LP, such as those with recent lumbar puncture, abnormal anatomy (scoliosis, spinal hardware), BMI >35 or other body habitus that would make landmark identification difficult.
Treatment
- Antibiotics: Empiric antibiotics should be started immediately, even before lumbar puncture results are available, to minimize the risk of brain damage or death. Common regimens include:
- Ceftriaxone or cefotaxime (for Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae), PLUS
- Vancomycin (to cover resistant Streptococcus pneumoniae).
- If gram negative rods are noted on gram stain, then ceftriaxone should be transitioned to meropenem for pseudomonas coverage.
- Ampicillin is used if Listeria monocytogenes is suspected (e.g., in neonates, immunocompromised patients, or older adults).
- Dexamethasone: In some cases, adjunctive dexamethasone can reduce neurological sequelae, particularly for Haemophilus influenzae (gram negative rods on gram stain).
- Most cases of viral meningitis resolve with supportive care, including hydration, pain management, and antipyretics.
- If HSV or VZV meningitis is suspected, intravenous acyclovir should be administered until testing returns.
- Most children presenting with meningitis will get empiric antibiotics while CSF cultures are pending, as there is no clear clinical differentiator between viral and bacterial meningitis and the risks of delayed treatment in bacterial meningitis are high.
- Fungal meningitis: Treatment with antifungal agents such as amphotericin B is required. Intrathecal antifungals are sometimes used as fungal meningitis can be difficult to treat.
- Tuberculous meningitis: Managed with a combination of anti-tubercular drugs (e.g., rifampin, isoniazid, pyrazinamide).
Potential complications
Meningitis can result in severe complications, particularly when treatment is delayed or ineffective:
- Seizures: Can occur in the acute phase or later as a result of brain injury.
- Hydrocephalus: Increased intracranial pressure due to obstructed cerebrospinal fluid (CSF) flow. This can be acute but also present well after the initial illness as grey-white matter scarring leads to obstruction of CSF flow and slow buildup of fluid.
- Cerebral edema: Swelling of the brain can cause life-threatening increased intracranial pressure. Cushing’s triad (bradycardia, hypertension, and irregular breathing) should immediately raise suspicion for increased intracranial pressure.
- Hearing loss: Particularly common after bacterial meningitis due to damage to the auditory nerve.
- Neurodevelopmental delay: Long-term cognitive, motor, and sensory deficits may result from brain injury caused by the infection.
- Stroke due to hypercoagulability or vasculitis.
Conclusion
Meningitis remains a significant cause of morbidity and mortality in pediatric patients. Prompt recognition and treatment are crucial to improving outcomes. Vaccination, timely diagnosis via lumbar puncture, and appropriate antibiotic or antiviral therapy are key to minimizing the risk of severe complications such as brain damage, hearing loss, and death. Pediatric residents and medical students must be familiar with the clinical presentation and management of meningitis to effectively care for these critically ill children.
- Tunkel, A. R., et al. (2017). Bacterial Meningitis in Adults: Diagnosis and Management. JAMA, 318(7), 706–717.
- van de Beek, D., et al. (2016). Bacterial Meningitis. Lancet, 388(10063), 528–537.
- Kaplan, S. L., & Mason, E. O. (2017). Meningitis in Children: Clinical Considerations. Pediatric Infectious Disease Journal, 36(7), 703–711.
- Smith, P. M., et al. (2019). Viral Meningitis: A Review of Etiology, Diagnosis, and Treatment. Pediatric Clinics of North America, 66(6), 1151–1166.
Image credits
Unless otherwise noted, images are from Adobe Stock.