At a glance......
- 1 Types of Meningitis
- 2 Pathophysiology
- 3 Causes of Meningitis
- 4 Symptoms of Meningitis
- 5 Diagnosis of Meningitis
- 5.1 Lumbar puncture
- 5.2 Cerebrospinal fluid cell count
- 5.3 Cerebrospinal fluid leukocyte differential
- 5.4 Cerebrospinal fluid biochemistry
- 5.5 Cerebrospinal fluid microscopy with Gram stain
- 5.6 Cerebrospinal fluid culture
- 5.7 Cerebrospinal fluid polymerase chain reaction
- 5.8 Blood tests
- 5.9 Swabs
- 5.10 Brain imaging
- 5.11 Common Tests Include The Following
- 6 Treatment
- 7 Treatment / Management
- 8 Prevention of Meningitis
- 9 References
Meningitis is inflammation of the meninges covering the brain. It is a pathological definition. The cerebrospinal fluid (CSF) typically exhibits an elevated number of leucocytes (or a pleocytosis). In adults, >5 leucocytes/μL is defined as elevated. Bacterial or viral meningitis is confirmed by the detection of a pathogen in the CSF. Bacterial meningitis may also be suggested by symptoms of meningism and appropriate bacteria in the blood.[rx]
Meningitis is an inflammation of the membranes (meninges) surrounding your brain and spinal cord. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs. Meningitis can be life-threatening because of the inflammation’s proximity to the brain and spinal cord; therefore, the condition is classified as a medical emergency.
Types of Meningitis
Meningitis caused by bacteria can be deadly and requires immediate medical attention. Vaccines are available to help protect against some kinds of bacterial meningitis.Streptococcus pneumoniae- A causative bacteria of meningitis.
The types of bacteria that cause bacterial meningitis vary according to the infected individual’s age group.
- In premature babies and newborns up to three months old, common causes are group B streptococci (subtypes III which normally inhabit the vagina and are mainly a cause during the first week of life) and bacteria that normally inhabit the digestive tract such as Escherichia coli (carrying the K1 antigen). Listeria monocytogenes (serotype IVb) is transmitted by the mother before birth and may cause meningitis in the newborn.
- Older children are more commonly affected by Neisseria meningitidis (meningococcus) and Streptococcus pneumoniae (serotypes 6, 9, 14, 18 and 23) and those under five by Haemophilus influenzae type B (in countries that do not offer vaccination).
- In adults, Neisseria meningitidis and Streptococcus pneumoniae together cause 80% of bacterial meningitis cases. Risk of infection with Listeria monocytogenes is increased in persons over 50 years old.The introduction of pneumococcal vaccine has lowered rates of pneumococcal meningitis in both children and adults.
- Recent skull trauma potentially allows nasal cavity bacteria to enter the meningeal space. Similarly, devices in the brain and meninges, such as cerebral shunts, extraventricular drains or Ommaya reservoirs, carry an increased risk of meningitis. In these cases, the persons are more likely to be infected with Staphylococci, Pseudomonas, and other Gram-negative bacteria.These pathogens are also associated with meningitis in people with an impaired immune system.
- Tuberculous meningitis, which is meningitis caused by Mycobacterium tuberculosis, is more common in people from countries in which tuberculosis is endemic, but is also encountered in persons with immune problems, such as AIDS.
- Meningitis caused by viruses is serious but often is less severe than bacterial meningitis. People with normal immune systems who get viral meningitis usually get better on their own. There are vaccines to prevent some kinds of viral meningitis.
- Viruses that cause meningitis include enteroviruses, herpes simplex virus (generally type 2, which produces most genital sores; less commonly type 1), varicella zoster virus (known for causing chickenpox and shingles), mumps virus, HIV, and LCMV. Mollaret’s meningitis is a chronic recurrent form of herpes meningitis; it is thought to be caused by herpes simplex virus type 2.
- Meningitis caused by fungi is rare, but people can get it by inhaling fungal spores from the environment. People with certain medical conditions, like diabetes, cancer, or HIV, are at higher risk of fungal meningitis.
- There are a number of risk factors for fungal meningitis, including the use of immunosuppressants (such as after organ transplantation), HIV/AIDS, and the loss of immunity associated with aging. It is uncommon in those with a normal immune system but has occurred with medication contamination.
- Symptom onset is typically more gradual, with headaches and fever being present for at least a couple of weeks before diagnosis. The most common fungal meningitis is cryptococcal meningitis due to Cryptococcus neoformans.
- In Africa, cryptococcal meningitis is now the most common cause of meningitis in multiple studies, and it accounts for 20–25% of AIDS-related deaths in Africa. Other less common fungal pathogens which can cause meningitis include: Coccidioides immitis, Histoplasma capsulatum, Blastomyces dermatitidis, and Candidaspecies.
- Various parasites can cause meningitis or can affect the brain or nervous system in other ways. Overall, parasitic meningitis is much less common than viral and bacterial meningitis.
- A parasitic cause is often assumed when there is a predominance of eosinophils (a type of white blood cell) in the CSF. The most common parasites implicated are Angiostrongylus cantonensis, Gnathostoma spinigerum, Schistosoma, as well as the conditions cysticercosis, toxocariasis, baylisascariasis, paragonimiasis, and a number of rarer infections and noninfective conditions.
Aseptic meningitis is a term referring to the broad category of meningitis that is not caused by bacteria. Approximately 50% of aseptic meningitis is due to viral infections. Other less common causes include
- drug reactions or allergies, and
- inflammatory diseases like lupus.
- Meningitis may occur as the result of several non-infectious causes: the spread of cancer to the meninges (malignant or neoplastic meningitis) and certain drugs (mainly non-steroidal anti-inflammatory drugs, antibiotics and intravenous immunoglobulins).
- It may also be caused by several inflammatory conditions, such as sarcoidosis (which is then called neurosarcoidosis), connective tissue disorders such as systemic lupus erythematosus, and certain forms of vasculitis (inflammatory conditions of the blood vessel wall), such as Behçet’s disease. Epidermoid cysts and dermoid cysts may cause meningitis by releasing irritant matter into the subarachnoid space.
- Primary amebic meningoencephalitis (PAM) is a rare and devastating infection of the brain caused by Naegleria fowleri. Naegleria fowleri is a free-living microscopic ameba that lives in warm water and soil.
Meningitis typically occurs through two routes of inoculation:
- Bacterial droplets colonize the nasopharynx and enter the bloodstream after the mucosal invasion. Upon making their way to the subarachnoid space, the bacteria cross the blood-brain barrier, causing a direct inflammatory and immune-mediated reaction.
Direct Contiguous Spread
- Organisms can enter the cerebrospinal fluid (CSF) via neighboring anatomic structures (otitis media, sinusitis), foreign objects (medical devices, penetrating trauma) or during operative procedures.
Viruses can penetrate the central nervous system (CNS) via retrograde transmission along neuronal pathways or by hematogenous seeding.
Causes of Meningitis
Several strains of bacteria can cause acute bacterial meningitis, most commonly
- Streptococcus pneumoniae (pneumococcus) – This bacterium is the most common cause of bacterial meningitis in infants, young children, and adults in the United States. It more commonly causes pneumonia or ear or sinus infections. A vaccine can help prevent this infection.
- Neisseria meningitidis (meningococcus) – This bacterium is another leading cause of bacterial meningitis. These bacteria commonly cause an upper respiratory infection but can cause meningococcal meningitis when they enter the bloodstream. This is a highly contagious infection that affects mainly teenagers and young adults. It may cause local epidemics in college dormitories, boarding schools, and military bases. A vaccine can help prevent infection.
- Haemophilus influenzae (Haemophilus) – Haemophilus influenza type b (Hib) bacterium was once the leading cause of bacterial meningitis in children. But new Hib vaccines have greatly reduced the number of cases of this type of meningitis.
- Listeria monocytogenes (listeria) – These bacteria can be found in unpasteurized cheeses, hot dogs and luncheon meats. Pregnant women, newborns, older adults and people with weakened immune systems are most susceptible.
- Fungal infection
- Autoimmune disorders
- Cancer medications
- Adults older than 60 years of age
- Children younger than 5 years of age
- People with alcoholism
- People with sickle cell anemia
- People with cancer, especially those receiving chemotherapy
- People who have received transplants and are taking drugs that suppress the immune system
- People with diabetes
- Those recently exposed to meningitis at home
- People living in close quarters (military barracks, dormitories)
- IV drug users
- People with shunts in place for hydrocephalus
Spreading the bacteria
The meningococcal bacteria that cause meningitis do not live long outside the body, so they are usually only spread through prolonged, close contact. Possible ways to spread the bacteria include:
- sharing utensils, such as cutlery
- sharing personal possessions, such as a toothbrush or cigarette
As most people, particularly adults above 25, have a natural immunity to the meningococcal bacteria, most cases of bacterial meningitis are isolated (single cases).
- a boarding school
- a university campus
- a military base
- student housing
Symptoms of Meningitis
Possible signs and symptoms in anyone older than the age of 2 include
- Sudden high fever
- Severe headache that seems different than normal
- Headache with nausea or vomiting
- Confusion or difficulty concentrating
- Stiff neck occurs in a majority of people with meningitis
- Fever and chills occur in most people with meningitis
- Vomiting occurs in many of people with meningitis
- Extreme sensitivity to bright lights (photophobia)
- History of a recent upper respiratory infection (for example, cold, sore throat)
- Sleepiness or difficulty waking
- Sensitivity to light
- No appetite or thirst
- Skin rash (sometimes, such as in meningococcal meningitis)
Signs of Meningitis in newborns
Newborns and infants may show these signs
- High fever
- Constant crying
- Be agitated and not want to be picked up
- Have a bulging soft spot on their head (fontanelle)
- Be floppy or unresponsive
- Have an unusually high-pitched cry
- Excessive sleepiness or irritability
- Inactivity or sluggishness
- Poor feeding
- A bulge in the soft spot on top of a baby’s head (fontanel)
- Stiffness in a baby’s body and neck
The Symptoms By Age
- Drowsiness or confusion;
- Severe headache;
- A stiff neck;
- Bright lights hurt the eyes; and
- Nausea and vomiting.
In babies younger than one year of age, symptoms of meningitis may be more difficult to identify. They may include:
- Fretfulness or irritability, especially when handled;
- Difficulty waking up;
- Difficulty feeding; and
A stiff neck and bulging of the fontanelle (soft spot on top of the skull) may occur in young babies with meningitis, but usually, these signs are not present early in the illness.
Each year there are over 1000 cases of bacterial meningitis in Canada. At least 50 species of bacteria can cause meningitis. Most cases are caused by one of the following bacteria:
- Meningococcus (scientific name Neisseria meningitis)
- Pneumococcus (scientific name Streptococcus pneumonia)
- Group B streptococcus (scientific name Streptococcus agalactiae)
- E coli (scientific name Escherichia coli)
The following are now uncommon causes of bacterial meningitis in Canada.
- H flu b or Hib (scientific name Haemophilus influenza type b)
- Listeria (Scientific name Listeria monocytogenes)
- Tuberculosis or TB (scientific name Mycobacterium tuberculosis)
Fungal meningitis is quite rare. The following types of fungus can cause meningitis.
- Candida albicans – is a fungus that normally causes thrush. In rare cases, the fungus can cause a dangerous form of meningitis, primarily in premature babies with very low birth weight or in persons with disorders of the immune system.
- Cryptococcus neoformans – is a fungus that is commonly found in soil. It causes most cases of fungal meningitis. It generally only occurs in people with AIDS, cancer or diabetes. It is life-threatening and requires treatment with antifungal drugs.
- Histoplasma – is a common fungus commonly found in soil in some parts of Canada. It can cause meningitis and other illnesses in people with disorders of the immune system (AIDS, cancer, etc).
Diagnosis of Meningitis
- Lumbar puncture is the key investigation. It enables rapid confirmation of meningitis and type of infecting organism. Diagnostic yield of LP can be diminished by collecting small CSF volumes. At least 10 mL can be safely removed.[rx,rx]
Cerebrospinal fluid cell count
- The cerebrospinal fluid remains one of the most rapidly informative tests. Pleocytosis indicates meningeal inflammation, of which infection is the most common cause. Van de Beek and colleagues reported that >90% of adults with bacterial meningitis had a CSF leukocyte count >100 cells/μL.[rx]
- Absence of pleocytosis makes meningitis much less likely, but does not completely rule it out. Approximately 1–2% of patients with bacterial meningitis will have a normal CSF leukocyte count. Positive pathogen detection and an absence of pleocytosis more frequently occurs among children, the immunocompromised, those pretreated with antibiotics or with mycobacteria tuberculosis infection.[rx]
Cerebrospinal fluid leukocyte differential
Cerebrospinal fluid leukocyte differential can help predict which type of pathogen is causing infection. Lymphocyte predominance suggests viral, while neutrophil predominance suggests bacterial infection. There are several exceptions to this general guide, including CSF neutrophil predominance observed in association with tuberculous meningitis
- Initial blood tests – should be performed for full blood count, coagulation studies, and electrolytes to assess for complications of sepsis and to guide fluid management. Serum glucose should be routinely measured as it may be low in the child with meningitis, contributing to seizures. Its measurement is also needed to accurately interpret the CSF glucose.
- Blood cultures – should be performed in all patients with suspected bacterial meningitis. They may be of particular value if a lumbar puncture is contraindicated. The likelihood of a positive blood culture result varies with the infecting organism; 40% of children with meningococcal meningitis will have a positive blood culture, whereas 50–90% of H. influenzae and 75% of S. pneumonia meningitis patients will have a positive culture result [rx].
- Both CRP and procalcitonin – have been evaluated to distinguish between viral and bacterial meningitis. Several studies have shown procalcitonin to have better diagnostic accuracy than CRP in differentiating between aseptic and bacterial meningitis [rx, rx]. Procalcitonin levels in combination with other clinical scoring systems have also been studied to evaluate the risk of bacterial meningitis [rx, rx]. Although potentially increasing the sensitivity of scoring systems, the use of procalcitonin in association with clinical scores to exclude the diagnosis of bacterial meningitis is not currently recommended
Cerebrospinal fluid biochemistry
- Cerebrospinal fluid glucose is normally approximately two-thirds of the blood (plasma) concentration. It is often lower in bacterial and tuberculous meningitis. As CSF glucose is influenced by the plasma glucose, it is essential to measure blood glucose at LP, to obtain an accurate CSF – blood glucose ratio. A CSF – blood glucose ratio <0.36 is an accurate (93%) marker for distinguishing bacterial from viral meningitis.[rx]
- Cerebrospinal fluid protein is normally <0.4 g/L. Elevated protein suggests inflammation. A CSF protein < 0.6 g/L largely rules out bacterial infection.[rx]
Cerebrospinal fluid microscopy with Gram stain
Cerebrospinal fluid culture
- Cerebrospinal fluid culture is historically regarded as the ‘gold standard’ for the diagnosis of bacterial meningitis. It is diagnostic in 70–85% of cases prior to antibiotic exposure. Sensitivity decreases by 20% following antibiotic pretreatment. Cerebrospinal fluid sterilization can occur within 2–4 hours of antibiotic administration for meningococci and pneumococci respectively.[rx] Lumbar puncture should be performed as soon as possible to maximize pathogen detection.
Cerebrospinal fluid polymerase chain reaction
- Cerebrospinal fluid polymerase chain reaction (PCR), using pathogen-specific nucleic acid sequences, can detect both bacteria and viruses with high sensitivity. The polymerase chain reaction is the ‘gold standard’ for the diagnosis of viral meningitis. The polymerase chain reaction is increasingly relied upon in bacterial meningitis. It has far greater sensitivity than culture in invasive meningococcal disease.17 Cerebrospinal fluid PCR is particularly valuable in patients who receive antibiotics before LP. Polymerase chain reaction for 16S ribosomal RNA (present in almost all bacteria) enables a broad screen for bacteria, but has lower sensitivity than pathogen-specific PCR.[rx,rx]
- Blood cultures should always be taken on admission and are helpful when antibiotics are started before LP. Blood cultures are positive in 50–80% of bacterial meningitis cases.[rx]
- Blood PCR is increasingly important, especially as PCR detects bacteria several days after antibiotic initiation.[rx] Blood PCR substantially increases the confirmation in meningococcal disease.[rx]
- Despite these tests, many patients will not have a cause identified for their meningitis.
- Blood biomarkers, such as procalcitonin and C-reactive protein, can help distinguish bacterial from viral meningitis in adults and can be used to help guide treatment if no aetiology is found.[rx,rx] Host biomarkers for detecting bacterial meningitis are being actively investigated by our Liverpool group and others. To date, there is insufficient evidence to recommend their routine use in the NHS.[rx]
- Throat, nasopharyngeal, and stool swabs are useful for detecting enteroviruses if the CSF PCR is negative.
- Brain imaging is neither obligatory in the management of meningitis nor a prerequisite to LP. Performing neuroimaging before LP is associated with delays in commencing antibiotics, which in turn can lead to an increase in mortality.[rx,rx] An urgent CT scan should be performed if there are clinical signs of brain shift. Clinical features indicative of a brain shift include focal neurological signs and reduced Glasgow Coma Score (GCS) [rx].
- The 2016 UK meningitis guidelines recommend an LP be performed without prior neuroimaging if the GCS is >12.[rx] Patients with a GCS ≤12 should be considered for critical care, intubation assessment, and neuroimaging. Imaging, particularly when contrast is used, may exhibit meningeal enhancement in meningitis. When brain shift is identified liaison with critical care and neurosurgical teams are essential.
Common Tests Include The Following
- Chest X-rays – can reveal the presence of pneumonia, tuberculosis, or fungal infections. Meningitis can occur after pneumonia.
- A CT scan – of the head may show problems like a brain abscess or sinusitis. Bacteria can spread from the sinuses to the meninges.
- MRI – to be oversure about meningitis
- Antibiotics – These are usually given intravenously.
- Corticosteroids – These may be given if inflammation is causing pressure in the brain, but studies show conflicting results.
- Acetaminophen, or paracetamol –Together with cool sponge baths, cooling pads, fluids, and room ventilation, these reduce fever.
- Anticonvulsants – If the patient has seizures, an anticonvulsant, such as phenobarbital or Dilantin, may be used.
- Oxygen therapy – Oxygen will be administered to assist with breathing.
- Fluids – Intravenous fluids can prevent dehydration, especially if the patient is vomiting or cannot drink.
- Sedatives – These will calm the patient if they are irritable or restless.
Blood tests may be used to monitor the patient’s levels of blood sugar, sodium, and other vital chemicals.
Treatment / Management
Managing the airway, maintaining oxygenation, giving sufficient intra-venous fluids while providing fever control are parts of the foundation of sepsis management.
The type of antibiotic is based on the presumed organism causing the infection. The clinician must take into account patient demographics and past medical history in order to provide the best antimicrobial coverage.
Current Empiric Therapy
Neonates – Up to 1 month old
- Ampicillin 100 mg/kg intravenously (IV) and
- Cefotaxime 75 mg/kg IV or Gentamicin 2.5 mg/kg IV and
- Acyclovir IV 40 mg/kg
More than 1 month old
- Ampicillin 50 mg/kg IV and
- Ceftriaxone 2 g IV and
- Acyclovir IV 40 mg/kg
Adults (18 to 49 years old)
- Ceftriaxone 2 g IV and
- Vancomycin 20 mg/kg IV
Adults older than 50 years old and the immunocompromised
- Ceftriaxone 2 g IV and
- Vancomycin 20 mg/kg IV and
- Ampicillin 2 g IV
Meningitis associated with a foreign body (post-procedure, penetrating trauma)
- Cefepime 2 g IV or Ceftazidime 2 g IV or Meropenem 2 g IV and
- Vancomycin 20 mg/kg IV
Meningitis with severe penicillin allergy
- Chloramphenicol 1 g IV and
- Vancomycin 20 mg/kg IV
Fungal (Cryptococcal) meningitis
- Amphotericin B 1 mg/kg IV and
- Flucytosine 25 mg/kg by mouth
- Third-generation cephalosporin
- Gram-negative coverage
- Very effective against S. pneumoniae and N. meningitides
- Better CNS penetration than Piperacillin-Tazobactam (typically used in gram-negative sepsis coverage)
- Gram-positive coverage (MRSA)
- Also used for resistant pneumococcus
- Listeria coverage (gram-positive bacilli)
- Is an aminopenicillin
- Fourth generation cephalosporin
- Increased activity against pseudomonas
- Third generation Cephalosporin
- Safe for neonates
Administration of dexamethasone 10 mg IV before or with the first dose of antibiotics has been shown to reduce the risk of morbidity and mortality, especially in the setting of S. pneumoniae infection.
It is important to note; the Infectious Disease Society of America recommends against dexamethasone if the patient has already received antibiotics.
Increased Intracranial Pressure
If the patient develops clinical signs of increased intracranial pressure, interventions to maintain cerebral perfusion include:
- Elevating the head of the bed to 30 degrees
- Inducing mild hyperventilation in the intubated patient
- Osmotic diuretics such as 25% mannitol or 3% saline
The transmission rate of N. meningitidis is 5% for close contacts, but chemoprophylaxis within 24 hours decreases that by 89%. Thus, chemoprophylaxis is indicated for close contacts of a patient suspected of having bacterial meningitis.
Close contacts include housemates, significant others, those who have shared utensils and health care providers in proximity to secretions (providing mouth-to-mouth resuscitation, intubating without a facemask).
Antibiotic chemoprophylaxis options include:
- Rifampin 10 mg/kg (max 200 mg/dose) every 12 hours for 4 doses or
- Ciprofloxacin 500 g orally once, or
- Ceftriaxone 250 mg intramuscularly once
Prevention of Meningitis
As several types of bacteria can cause bacterial meningitis, so a range of vaccines is necessary to prevent infection.
- Haemophilus influenzae type b – can be prevented with Hib immunisation, which is available in combination vaccines free on the National Immunisation Program Schedule. It is routinely offered tor babies and needs to be purchased on prescription for some groups at high risk of bacterial disease.
- Meningococcal group A, B, C, W135 and Y – can be prevented with a range of vaccines. Some immunisation is available free on the National Immunisation Program Schedule routinely for 12 month old babies or childhood catch-up and some vaccine needs to be purchased with prescription for some groups at high risk of bacterial disease or some travellers
- Pneumococcal – can be prevented with two types of pneumococcal vaccine.. They are available free on the National Immunisation Schedule to all babies and adults 50 years of age, if the person is an Aboriginal or Torres Strait Islander, or at 65 years of age and over. They need to be purchased on prescription for some groups at high risk of bacterial disease.
- A survey of 17 million people in the U.S. found that the incidence of all types of meningitis fell by 31 percent from 1998 to 2007, after the introduction of routine vaccinations against meningitis-causing bacteria.
- The meningococcal vaccine is the primary vaccine in the U.S. All children should have this at the age of 11 to 12 years and again at 16 years, when the risk of infection is higher.
- The Hib vaccine protects children against H. Influenzae. Before its introduction in the U.S. in 1985, H. Influenzae infected over 20,000 children under 5 years annually, with a 3 to 6 percent mortality rate. Widespread vaccination has reduced the incidence of bacterial meningitis by over 99 percent.
- The Hib vaccine is given in four doses at the ages of 2, 4, 6, and 12 to 15 months.
For patients treated promptly, the prognosis is good. However, patients who present with an altered state of consciousness have a high morbidity and mortality. Some patients may develop seizures during the illness, which are very difficult to control or are prolonged. Any patient with a residual neurological deficit after meningitis treatment is also left with a disability. Patients art the greatest risk for death usually have the following features:
- Advanced aged
- Low GCS
- CSF WBC count which is low
- Gram-positive cocci in the CSF
Serious complications in survivors include:
- Hearing loss
- Cranial nerve palsies
- Cognitive dysfunction
- Cortical blindness
- Focal paralysis