Meningitis

Definition

Meningitis is inflammation of the meninges, the membranes that surround the brain and spinal cord. Meningitis is a rare disease caused mainly by viral infection but also by bacterial or fungal infections. Injuries, allergies, cancer, and certain drugs (e.g., eculizumab) can also cause meningitis. The disease can be spread between individuals and can be life-threatening. Viral meningitis, also called aseptic meningitis, is the most prevalent type.

Description

The brain and spinal cord are encased in three layers of membranes called the meninges. The purpose of the meninges is to protect and insulate the brain and nerves of the central nervous system. The space between the inner membranes contains cerebrospinal fluid (CSF), a lubricating and nutritive fluid that bathes the brain and the spinal cord and helps insulate the central nervous system from trauma. Many blood vessels, as well as peripheral and cranial nerves, pass through this space. The inflammation and swelling of the meninges that occur in meningitis can damage and destroy brain tissue, injure nerves, and interrupt nervous system function, compromise blood flow to the brain, and interfere with CSF production and reabsorption.

Most meningitis cases are caused by viruses, bacteria, or fungi that enter the bloodstream. The organisms are carried to the meninges where they prompt an immune response that leads to inflammation and infection. Non-infectious meningitis can be caused by allergies, cancers, certain drugs, or autoimmune diseases that have a neurological (central nervous system) component (e.g., sarcoidosis, lupus, and vasculitis). Outbreaks of viral and bacterial meningitis have occurred in childcare centers, college dormitories, and military bases where there is close human contact. Viral meningitis, the most prevalent type, is less severe than bacterial meningitis, is rarely fatal, and may resolve without treatment. Bacterial meningitis, by contrast, is a medical emergency and has a high fatality rate if untreated.

Fungal meningitis occurs only rarely but may sometimes develop as an opportunistic infection in immunocompromised HIV/AIDS patients. However, in the United States in 2012, a major fungal meningitis outbreak was linked to one or more contaminated injectable drugs from a compounding pharmacy, infecting 753 individuals in 20 states and causing 643 deaths.

Risk factors

Children and young adults, especially those in group living situations, are at greatest risk for meningitis. Newborn boys are at three times the risk of newborn girls. Risk is also higher in pregnant women and patients with a weakened immune system due to HIV/AIDS, diabetes, recent organ transplant, or spleen removal (splenectomy). People who work with animals are at an increased risk for meningitis caused by Listeria monocytogenes bacteria. Exposure to Listeria may also increase risk in newborns, older adults, and individuals with chronic illness or compromised immune function. Sexually transmitted meningitis is rare although individuals who have had untreated syphilis or other sexually transmitted disease may be at increased risk for either bacterial or viral meningitis.

Demographics

HATTIE ALEXANDER (1901–1968)

Hattie Alexander, a dedicated pediatrician, medical educator, and researcher in microbiology, won international recognition for deriving a serum to combat influenzal meningitis, a common disease that was nearly always fatal to infants and young children. Alexander subsequently investigated microbiological genetics and the processes whereby bacteria, through genetic mutation, acquire resistance to antibiotics. In 1964, as president of the American Pediatric Society, she became one of the first women to head a national medical association.

As an intern at the Harriet Lane Home of Johns Hopkins Hospital from 1930 to 1931, Alexander became interested in influenzal meningitis. The source of the disease was Haemophilus influenzae, a bacteria that causes inflammation of the meninges, the membranes surrounding the brain and spinal cord. In 1931, Alexander began a second internship at the Babies Hospital of the Columbia- Presbyterian Medical Center in New York City. There, she witnessed firsthand the futility of medical efforts to save babies who had contracted influenzal meningitis.

Alexander's early research focused on deriving a serum (the liquid portion of blood that contains antibodies) that would be effective against influenzal meningitis. Sera derived from animals that have been exposed to a specific diseaseproducing bacterium often contain antibodies against the disease and can be developed for use in immunizing humans against it. Alexander knew that the Rockefeller Institute in New York City had been able to prepare a rabbit serum for the treatment of pneumonia, another bacterial disease. Therefore, Alexander experimented with rabbit sera and, by 1939, was able to announce the development of a rabbit serum effective in curing infants of influenzal meningitis.

In the early 1940s, Alexander experimented with the use of drugs in combination with rabbit serum for the treatment of influenzal meningitis. Within the next two years, she saw infant deaths due to the disease drop by 80%.

Meningitis rates in developing countries are estimated to be at least ten times higher than in the United States, Canada, and Europe. This is believed to be due to the availability of vaccines in the developed countries and the lack thereof in developing countries. Periodic epidemics that occur in sub-Saharan Africa and parts of India are directly attributed to lack of access to vaccines.

Causes and symptoms

Meningitis is caused by infection from viruses, bacteria, or fungi. It is highly contagious and easily passed from one individual to another through direct contact or exposure through coughs, sneezes, or shared objects. It can also result from the spread of an untreated infection elsewhere in the body through the bloodstream. In order for this spread to occur, enough disease-causing organisms must be able to cross the blood-brain barrier or the infected tissue must be located close to the meninges, such as with a severe, poorly treated ear or sinus infection, or a skull fracture. Insect and animal bites can also inject disease-causing organisms directly into the bloodstream. Although uncommon, virus infections such as herpes simplex can spread along a nerve to the spinal cord and brain, resulting in viral meningitis.

Disease agents

About 30% of viral meningitis cases in the United States are caused by enteroviruses that normally live in the human digestive tract, although the specific virus responsible for causing a meningitis case is often not identified. Enteroviruses are found in saliva, throat mucus, and feces, and they can be transmitted through direct contact with an infected person or a contaminated object or surface. Many other viruses, including those that cause mumps, measles, polio, and chickenpox, along with West Nile, herpes simplex, and La Crosse viruses, can cause meningitis. Viral meningitis is usually a mild illness that often resolves within two weeks without any specific treatment.

Bacterial meningitis can be transmitted by airborne droplets from coughs and sneezes, as well as by kisses. Most cases of bacterial meningitis are caused by one of four bacteria:

Bacterial meningitis is often acute, developing in less than 24 hours. Subacute meningitis, caused by bacteria or viruses, develops over one to seven days. Chronic meningitis, which is rare, develops over a period of weeks. It may have a noninfectious cause and be due to a slow-growing fungus that invades the meninges and CSF. Cryptococcal meningitis is a life-threatening fungal disease that affects HIV/AIDS patients and others with immune system dysfunction.

Symptoms

The symptoms of meningitis are almost always high fever, stiff neck, and severe headache. Wide variations can occur in symptoms. Although older adults are at higher risk of developing acute bacterial meningitis than younger adults, older adults with comorbid chronic disease may not develop fever or other obvious meningitis symptoms but will still have an earlier and higher mortality rate. Meningitis symptoms in adults may also include:

Infants may not develop a fever, and seizures may be the primary symptom of meningitis. Other symptoms in infants and young children may include:

KEY TERMS
Aseptic meningitis—
A term for meningitis not caused by bacteria.
Blood-brain barrier—
The arrangement of blood vessels in the brain that prevents many substances from passing from the blood into brain tissues.
Cerebrospinal fluid (CSF)—
Fluid produced within chambers of the brain that bathes brain and spinal cord surfaces.
Enteroviruses—
A family of viruses that normally live in the digestive tract and that can cause viral meningitis.
Hib—
Conjugate vaccine; a vaccine that immunizes infants and children against Haemophilus influenzae that cause meningitis and pneumonia.
Lumbar puncture—
Spinal tap; a procedure in which a thin needle is inserted between the vertebrae of the lower back to obtain a sample of cerebrospinal fluid for laboratory testing.
Meninges (singular, meninx)—
The membranes that surround the brain and spinal cord.
Meningococcal meningitis—
Highly contagious meningitis caused by the bacterium Neisseria meningitidis.
Opportunistic infection—
An infection that usually occurs only in individuals with a suppressed immune system.
Outbreak—
A sudden increase in the incidence of a specific disease.
Pneumococcal meningitis—
Meningitis caused by the bacterium Streptococcus pneumoniae.
Stroke—
The death of cells and loss of neurologic function in an area of brain tissue where blood circulation is obstructed and brain cells are deprived of oxygen. Stroke occurs either as a result of a blood clot in a blood vessel that carries blood to the brain (ischemic stroke) or rupture of a weakened area of a blood vessel (brain aneurysm). Stroke may result in sudden diminishing or loss of consciousness, sensation, and/or voluntary movement.

Diagnosis

Several physical maneuvers may help to confirm meningitis as follows:

A lumbar puncture (spinal tap) will be done by inserting a needle into vertebrae of the spinal column at the lower back to withdraw CSF for testing. The presence of infection-fighting white blood cells and excess protein (albumin) in the CSF is an indication of meningitis. A low plasma glucose level suggests bacterial meningitis. A culture of the CSF may help to identify the causal organism. A sample of mucus from the throat may be obtained by throat swab for culture as well. A rapid CSF test to detect viral DNA can accurately identify about 90% of viral meningitis cases in less than three hours. If no virus is identified, and culture results are not yet available, the disease will be treated immediately with broad spectrum antibiotics against a potential bacterial cause for meningitis.

A computed tomography (CT) scan may detect signs of inflammation of the meninges. Magnetic resonance imaging (MRI) is a more sensitive imaging technique that can examine tissue in more detail and can help to rule out head trauma, stroke, tumors, and blood clots in the brain.

Newer automated multiplex polymerase chain reaction (PCR) methods were being developed as of 2018 to improve the microbiological diagnosis of infectious meningitis.

Treatment

Bacterial meningitis is a life-threatening emergency that requires emergent treatment in the hospital setting. Prompt antibiotic treatment is noted to save lives and intravenous penicillin or other broad-spectrum antibiotic will be given even before culture results are available. Study results showed a 30% increase in death or neurological damage for every hour that antimicrobial treatment was delayed. Patients also may need treatment to reduce brain swelling or for shock or seizures. Fluid may be drained from the sinuses or from the space between the meninges and the brain to relieve pressure caused by swelling of tissue. Intravenous fluids will be needed to treat dehydration and oxygen to assist breathing. Once the causal bacterial agent has been identified, treatment usually proceeds with a combination of antibiotics shown to be effective for the specific bacterium. Selection of antibiotics can be difficult because of increasing antibiotic resistance among pathogens. For example, fluoroquinolone-resistant N. meningitidis was first reported in the United States in 2007, and cephalosporins are used instead, including cefotaxime (Claforan) and ceftriaxone (Rocephin). Other drugs used for bacterial meningitis are penicillin-type antibiotics or aminoglycoside drugs such as gentamicin. Dexamethasone therapy is implemented as an adjunctive treatment for adults with pneumococcal meningitis.

Viral meningitis is usually treated at home with a few weeks of bed rest. Patients can take over-the-counter pain relievers for muscle aches and pains and to reduce fever. Antiviral drugs may be used to treat an existing herpes infection.

Antifungal medications for meningitis are shown to have harmful side effects, so treatment may be deferred until a fungal cause is identified definitively. Non-infectious meningitis from an allergic reaction or comorbid autoimmune disease may be treated with short-term corticosteroid medications. Sometimes these conditions resolve without treatment.

Public health role and response

Prognosis

Prognosis depends on the cause of the meningitis, the age and overall health status of the individual, and the response to treatment. Adequate and prompt treatment of bacterial meningitis is critical in terms of patient outcomes. Patients with bacterial meningitis may improve within 48–72 hours after prompt antibiotic treatment; however, complications of bacterial meningitis are typically more serious. Neonatal bacterial meningitis is not common but has a poor prognosis with high morbidity and mortality. Acute bacterial meningitis has a mortality rate of 10%–15% even with treatment, and 10%–20% of survivors have complications such as blindness, hearing loss, learning disorders, speech problems, memory problems, behavior problems, brain damage, or paralysis. The longer treatment is delayed, the greater the risk for seizures or permanent neurological damage. In contrast, patients with viral meningitis usually recover within two to four weeks, sometimes without treatment. Complications are rare, and the mortality rate is less than 1%. Fungal meningitis is uncommon and standard treatment is usually effective.

Prevention

Routine immunization against Hib, pneumococcus, and serogroup C meningococcus has reduced the incidence of meningitis cause by these bacteria. The Hib vaccine for H. influenzae meningitis and pneumococcal conjugate vaccine (PCV7) are included in regular statewide childhood immunization schedules in the United States. Pneumococcal polysaccharide vaccine (PPSV) is given to older children and adults. The meningococcal conjugate vaccine (MCV4) is recommended for all children at ages 11–12. Adults over 55 are immunized with a similar vaccine called MPSV4. Effective vaccines have been developed against all of the bacteria that usually cause meningococcal meningitis in the United States, which accounts for 50% of all cases. In June 2015, the FDA licensed two serogroup B meningococcal vaccines (Bexsero, Trumenba), which are recommended for children and young adults aged 10 to 25 who already have meningococcal infections, those at risk because of an outbreak or working with N. meningitidis, or those taking the drug eculizumab (Soliris). Changes were made to the dosages in 2016, but otherwise both vaccines are available. Clinical trials evaluating other vaccines were ongoing as of 2018.

QUESTIONS TO ASK YOUR DOCTOR

Other preventive measures against contagious meningitis include:

See also Escherichia coli; Viruses.

Resources

BOOKS

Christodoulides, Myron. Meningitis: Cellular and Molecular Basis.. Wallingford, UK: CABI (Center for Agriculture and Bioscience International), 2013.

Feavers, Ian, Andrew J. Pollard, and Manish Sadarangani, editors. Handbook of Meningococcal Disease Management.. New York: Springer, 2017.

PERIODICALS

Charalambous, L. T., A. Premji, C. Tybout, et al. “Prevalence, Healthcare Resource Utilization and Overall Burden of Fungal Meningitis in the United States.” Journal of Medical Microbiology 959 (February 2018): 215–27.

Griffiths, M. J., F. McGill, and T. Solomon. “Bacterial Meningitis.” Management of Acute Meningitis 18 (March 2018): 164–69.

Heckenberg, S. G., M. C. Brouwer, and D. van de Beeke. “Bacterial Meningitis.” Handbook of Clinical Neurology 121 (March 2014): 1361–75.

Ku, L. C., K A. Boggess, and M. Cohen-Wolkowiez. “Bacterial Meningitis in Infants.” Clinical Perinatology 42 (March 2015): 29–45.

WEBSITES

Centers for Disease Control and Prevention. “Multistate Outbreak of Fungal Meningitis and Other Infections.” https://www.cdc.gov/hai/outbreaks/meningitis.html (accessed April 29, 2018).

Mayo Clinic staff. “Meningitis.” MayoClinic.org . http://www.mayoclinic.com/diseases-conditions/meningitis/symptoms-causes/syc-20350508 (accessed April 16, 2018).

MedlinePlus. “Meningitis.” http://www.medlineplus.gov/meningitis.htmlnlm.nih.gov/medlineplus/meningitis.html (accessed April 16, 2018).

http://www.ninds.nih.gov/disorders/all-disorders/meningitis-and-encephalitis-information-page (accessed April 16, 2018).

ORGANIZATIONS

Immunization Action Coalition, 2550 University Ave. West, Ste. 415 North, St. Paul, MN, 55114, 1(651) 647-9009, Fax: 1(651) 647-9131, admin@immunize.org, http://www.immunize.org .

National Institute of Allergy and Infectious Diseases, Office of Communications and Government Relations, 6610 Rockledge Dr., MSC 6612, Bethesda, MD, 20892-6612, (301) 496-5717, Fax: (301) 402-3573, (866) 284-4107, ocpostoffice@niaid.nih.gov, http://www.niaid.nih.gov .

National Meningitis Association, PO Box 60143, Ft. Myers, FL, 33906, (866) 366-3662), Fax: (877) 703-6096, http://www.nmaus.org .

U.S. Centers for Disease Control and Prevention, 1600 Clifton Rd., Atlanta, GA, 30333, (800) 232-4636, cdcinfo@cdc.gov, http://www.cdc.gov .

U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20993-0002, (888) 463-6332), http://www.fda.gov .

World Health Organization, Avenue Appia 20, 1211 Geneva, Switzerland, 27, 41 22 791-2111, Fax: 41 22 791-3111, info@who.int, http://www.who.int/en .

Helen Colby, MS
Revised by L. Lee Culvert

  This information is not a tool for self-diagnosis or a substitute for professional care.