Meningitis
Meningitis | |
---|---|
Frequency | 7.7 million (2019)[9] |
Deaths | 236,000 (2019)[9] |
Meningitis is
Other symptoms include
The inflammation may be caused by infection with
Some forms of meningitis are preventable by
In 2019, meningitis was diagnosed in about 7.7 million people worldwide,
Signs and symptoms
Clinical features
In adults, the most common symptom of meningitis is a severe headache, occurring in almost 90% of cases of bacterial meningitis, followed by neck stiffness (the inability to flex the neck forward passively due to increased neck muscle tone and stiffness).[16] The classic triad of diagnostic signs consists of neck stiffness, sudden high fever, and altered mental status; however, all three features are present in only 44–46% of bacterial meningitis cases.[16][17] If none of the three signs are present, acute meningitis is extremely unlikely.[17] Other signs commonly associated with meningitis include photophobia (intolerance to bright light) and phonophobia (intolerance to loud noises). Small children often do not exhibit the aforementioned symptoms, and may only be irritable and look unwell.[2] The fontanelle (the soft spot on the top of a baby's head) can bulge in infants aged up to 6 months. Other features that distinguish meningitis from less severe illnesses in young children are leg pain, cold extremities, and an abnormal skin color.[18][19]
Neck stiffness occurs in 70% of bacterial meningitis in adults.
Other problems can produce symptoms similar to those above, but from non-meningitic causes. This is called meningism or pseudomeningitis.[21]
Meningitis caused by the bacterium
Early complications
Additional problems may occur in the early stage of the illness. These may require specific treatment, and sometimes indicate severe illness or worse prognosis. The infection may trigger
The
Inflammation of the meninges may lead to abnormalities of the
Causes
Meningitis is typically caused by an
Bacterial
The types of bacteria that cause bacterial meningitis vary according to the infected individual's age group.
- In 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) can be contracted when consuming improperly prepared food such as dairy products, produce and deli meats,[25][26] and may cause meningitis in the newborn.[27]
- 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).[2][8]
- In adults, Neisseria meningitidis and Streptococcus pneumoniae together cause 80% of bacterial meningitis cases. Risk of infection with Listeria monocytogenes is increased in people over 50 years old.[3][8] The introduction of pneumococcal vaccine has lowered rates of pneumococcal meningitis in both children and adults.[28]
A
Recurrent bacterial meningitis may be caused by persisting anatomical defects, either
Viral
Viruses that cause meningitis include
Fungal
There are a number of risk factors for
Parasitic
A
Rarely, free-living parasitic
Non-infectious
Meningitis may occur as the result of several non-infectious causes: spread of
Mechanism
The meninges comprise three membranes that, together with the
In bacterial meningitis, bacteria reach the meninges by one of two main routes: through the bloodstream (hematogenous spread) or through direct contact between the meninges and either the nasal cavity or the skin. In most cases, meningitis follows invasion of the bloodstream by organisms that live on
The large-scale inflammation that occurs in the subarachnoid space during meningitis is not a direct result of bacterial infection but can rather largely be attributed to the response of the immune system to the entry of bacteria into the central nervous system. When components of the bacterial cell membrane are identified by the immune cells of the brain (astrocytes and microglia), they respond by releasing large amounts of cytokines, hormone-like mediators that recruit other immune cells and stimulate other tissues to participate in an immune response. The blood–brain barrier becomes more permeable, leading to "vasogenic" cerebral edema (swelling of the brain due to fluid leakage from blood vessels). Large numbers of white blood cells enter the CSF, causing inflammation of the meninges and leading to "interstitial" edema (swelling due to fluid between the cells). In addition, the walls of the blood vessels themselves become inflamed (cerebral vasculitis), which leads to decreased blood flow and a third type of edema, "cytotoxic" edema. The three forms of cerebral edema all lead to increased intracranial pressure; together with the lowered blood pressure often encountered in sepsis, this means that it is harder for blood to enter the brain; consequently brain cells are deprived of oxygen and undergo apoptosis (programmed cell death).[2]
Administration of antibiotics may initially worsen the process outlined above, by increasing the amount of bacterial cell membrane products released through the destruction of bacteria. Particular treatments, such as the use of corticosteroids, are aimed at dampening the immune system's response to this phenomenon.[2][3]
Diagnosis
Type of meningitis | Glucose | Protein
|
Cells |
---|---|---|---|
Acute bacterial | low | high | PMNs, often > 300/mm3 |
Acute viral | normal | normal or high | mononuclear, < 300/mm3 |
Tuberculous | low | high | mononuclear and PMNs, < 300/mm3 |
Fungal | low | high | < 300/mm3 |
Malignant | low | high | usually mononuclear |
Diagnosing meningitis as promptly as possible can improve outcomes.
There are no physical tests that can rule out or determine if a person has meningitis.[50] The jolt accentuation test is not specific or sensitive enough to completely rule out meningitis.[50]
If someone is suspected of having meningitis, blood tests are performed for markers of inflammation (e.g. C-reactive protein, complete blood count), as well as blood cultures.[8][48] If a CT or MRI is required before LP, or if LP proves difficult, professional guidelines suggest that antibiotics should be administered first to prevent delay in treatment,[8] especially if this may be longer than 30 minutes.[48][49] Often, CT or MRI scans are performed at a later stage to assess for complications of meningitis.[2]
In severe forms of meningitis, monitoring of blood electrolytes may be important; for example,
Lumbar puncture
A lumbar puncture is done by positioning the person, usually lying on the side, applying
The CSF sample is examined for presence and types of
The concentration of glucose in CSF is normally above 40% of that in blood. In bacterial meningitis it is typically lower; the CSF glucose level is therefore divided by the
Various other specialized tests may be used to distinguish between different types of meningitis. A
A diagnostic and therapeutic difficulty is "partially treated meningitis", where there are meningitis symptoms after receiving antibiotics (such as for presumptive sinusitis). When this happens, CSF findings may resemble those of viral meningitis, but antibiotic treatment may need to be continued until there is definitive positive evidence of a viral cause (e.g. a positive enterovirus PCR).[22]
Postmortem
Meningitis can be diagnosed after death has occurred. The findings from a
Prevention
For some causes of meningitis, protection can be provided in the long term through vaccination, or in the short term with antibiotics. Some behavioral measures may also be effective.
Behavioral
Bacterial and viral meningitis are contagious, but neither is as contagious as the
Vaccination
Since the 1980s, many countries have included immunization against Haemophilus influenzae type B in their routine childhood vaccination schemes. This has practically eliminated this pathogen as a cause of meningitis in young children in those countries. In the countries in which the disease burden is highest, however, the vaccine is still too expensive.[59][60] Similarly, immunization against mumps has led to a sharp fall in the number of cases of mumps meningitis, which prior to vaccination occurred in 15% of all cases of mumps.[22]
Meningococcus vaccines exist against groups A, B, C, W135 and Y.[61][62][63] In countries where the vaccine for meningococcus group C was introduced, cases caused by this pathogen have decreased substantially.[59] A quadrivalent vaccine now exists, which combines four vaccines with the exception of B; immunization with this ACW135Y vaccine is now a visa requirement for taking part in Hajj.[64] Development of a vaccine against group B meningococci has proved much more difficult, as its surface proteins (which would normally be used to make a vaccine) only elicit a weak response from the immune system, or cross-react with normal human proteins.[59][61] Still, some countries (New Zealand, Cuba, Norway and Chile) have developed vaccines against local strains of group B meningococci; some have shown good results and are used in local immunization schedules.[61] Two new vaccines, both approved in 2014, are effective against a wider range of group B meningococci strains.[62][63] In Africa, until recently, the approach for prevention and control of meningococcal epidemics was based on early detection of the disease and emergency reactive mass vaccination of the at-risk population with bivalent A/C or trivalent A/C/W135 polysaccharide vaccines,[65] though the introduction of MenAfriVac (meningococcus group A vaccine) has demonstrated effectiveness in young people and has been described as a model for product development partnerships in resource-limited settings.[66][67]
Routine vaccination against Streptococcus pneumoniae with the
Antibiotics
Short-term antibiotic prophylaxis is another method of prevention, particularly of meningococcal meningitis. In cases of meningococcal meningitis, preventative treatment in close contacts with antibiotics (e.g. rifampicin, ciprofloxacin or ceftriaxone) can reduce their risk of contracting the condition, but does not protect against future infections.[48][69] Resistance to rifampicin has been noted to increase after use, which has caused some to recommend considering other agents.[69] While antibiotics are frequently used in an attempt to prevent meningitis in those with a basilar skull fracture there is not enough evidence to determine whether this is beneficial or harmful.[70] This applies to those with or without a CSF leak.[70]
Management
Meningitis is potentially life-threatening and has a high mortality rate if untreated;
Mechanical ventilation may be needed if the level of consciousness is very low, or if there is evidence of respiratory failure. If there are signs of raised intracranial pressure, measures to monitor the pressure may be taken; this would allow the optimization of the cerebral perfusion pressure and various treatments to decrease the intracranial pressure with medication (e.g. mannitol).[3] Seizures are treated with anticonvulsants.[3] Hydrocephalus (obstructed flow of CSF) may require insertion of a temporary or long-term drainage device, such as a cerebral shunt.[3] The osmotic therapy, glycerol, has an unclear effect on mortality but may decrease hearing problems.[72]
Bacterial meningitis
Antibiotics
Empirical therapy may be chosen on the basis of the person's age, whether the infection was preceded by a head injury, whether the person has undergone recent neurosurgery and whether or not a cerebral shunt is present.[8] In young children and those over 50 years of age, as well as those who are immunocompromised, the addition of ampicillin is recommended to cover Listeria monocytogenes.[8][48] Once the Gram stain results become available, and the broad type of bacterial cause is known, it may be possible to change the antibiotics to those likely to deal with the presumed group of pathogens.[8] The results of the CSF culture generally take longer to become available (24–48 hours). Once they do, empiric therapy may be switched to specific antibiotic therapy targeted to the specific causative organism and its sensitivities to antibiotics.[8] For an antibiotic to be effective in meningitis it must not only be active against the pathogenic bacterium but also reach the meninges in adequate quantities; some antibiotics have inadequate penetrance and therefore have little use in meningitis. Most of the antibiotics used in meningitis have not been tested directly on people with meningitis in clinical trials. Rather, the relevant knowledge has mostly derived from laboratory studies in rabbits.[8] Tuberculous meningitis requires prolonged treatment with antibiotics. While tuberculosis of the lungs is typically treated for six months, those with tuberculous meningitis are typically treated for a year or longer.[31]
Fluid therapy
Fluid given intravenously are an essential part of treatment of bacterial meningitis. There is no difference in terms of mortality or acute severe neurological complications in children given a maintenance regimen over restricted-fluid regimen, but evidence is in favor of the maintenance regimen in terms of emergence of chronic severe neurological complications.[74]
Steroids
Additional treatment with
Professional guidelines therefore recommend the commencement of dexamethasone or a similar corticosteroid just before the first dose of antibiotics is given, and continued for four days.[48][49] Given that most of the benefit of the treatment is confined to those with pneumococcal meningitis, some guidelines suggest that dexamethasone be discontinued if another cause for meningitis is identified.[8][48] The likely mechanism is suppression of overactive inflammation.[78]
Additional treatment with corticosteroids have a different role in children than in adults. Though the benefit of corticosteroids has been demonstrated in adults as well as in children from high-income countries, their use in children from low-income countries is not supported by the evidence; the reason for this discrepancy is not clear.[75] Even in high-income countries, the benefit of corticosteroids is only seen when they are given prior to the first dose of antibiotics, and is greatest in cases of H. influenzae meningitis,[8][79] the incidence of which has decreased dramatically since the introduction of the Hib vaccine. Thus, corticosteroids are recommended in the treatment of pediatric meningitis if the cause is H. influenzae, and only if given prior to the first dose of antibiotics; other uses are controversial.[8]
Adjuvant therapies
In addition to the primary therapy of antibiotics and corticosteroids, other adjuvant therapies are under development or are sometimes used to try and improve survival from bacterial meningitis and reduce the risk of neurological problems. Examples of adjuvant therapies that have been trialed include acetaminophen, immunoglobulin therapy, heparin, pentoxifyline, and a mononucleotide mixture with succinic acid.[80] It is not clear if any of these therapies are helpful or worsen outcomes in people with acute bacterial meningitis.[80]
Viral meningitis
Viral meningitis typically only requires supportive therapy; most viruses responsible for causing meningitis are not amenable to specific treatment. Viral meningitis tends to run a more benign course than bacterial meningitis. Herpes simplex virus and varicella zoster virus may respond to treatment with antiviral drugs such as aciclovir, but there are no clinical trials that have specifically addressed whether this treatment is effective.[22] Mild cases of viral meningitis can be treated at home with conservative measures such as fluid, bedrest, and analgesics.[81]
Fungal meningitis
Fungal meningitis, such as
Prognosis
Untreated, bacterial meningitis is almost always fatal. According to the WHO bacterial meningitis has an overall mortality rate of 16.7% (with treatment).[12] Viral meningitis, in contrast, tends to resolve spontaneously and is rarely fatal. With treatment, mortality (risk of death) from bacterial meningitis depends on the age of the person and the underlying cause. Of newborns, 20–30% may die from an episode of bacterial meningitis. This risk is much lower in older children, whose mortality is about 2%, but rises again to about 19–37% in adults.[2][3]
Risk of death is predicted by various factors apart from age, such as the pathogen and the time it takes for the pathogen to be cleared from the cerebrospinal fluid,[2] the severity of the generalized illness, a decreased level of consciousness or an abnormally low count of white blood cells in the CSF.[3] Meningitis caused by H. influenzae and meningococci has a better prognosis than cases caused by group B streptococci, coliforms and S. pneumoniae.[2] In adults, too, meningococcal meningitis has a lower mortality (3–7%) than pneumococcal disease.[3]
In children there are several potential disabilities which may result from damage to the nervous system, including sensorineural hearing loss, epilepsy, learning and behavioral difficulties, as well as decreased intelligence.[2] These occur in about 15% of survivors.[2] Some of the hearing loss may be reversible.[84] In adults, 66% of all cases emerge without disability. The main problems are deafness (in 14%) and cognitive impairment (in 10%).[3]
Tuberculous meningitis in children continues to be associated with a significant risk of death even with treatment (19%), and a significant proportion of the surviving children have ongoing neurological problems. Just over a third of all cases survives with no problems.[85]
Epidemiology
Although meningitis is a
Bacterial meningitis occurs in about 3 people per 100,000 annually in Western countries. Population-wide studies have shown that viral meningitis is more common, at 10.9 per 100,000, and occurs more often in the summer. In Brazil, the rate of bacterial meningitis is higher, at 45.8 per 100,000 annually.[17] Sub-Saharan Africa has been plagued by large epidemics of meningococcal meningitis for over a century,[88] leading to it being labeled the "meningitis belt". Epidemics typically occur in the dry season (December to June), and an epidemic wave can last two to three years, dying out during the intervening rainy seasons.[89] Attack rates of 100–800 cases per 100,000 are encountered in this area,[90] which is poorly served by medical care. These cases are predominantly caused by meningococci.[17] The largest epidemic ever recorded in history swept across the entire region in 1996–1997, causing over 250,000 cases and 25,000 deaths.[91]
Meningococcal disease occurs in epidemics in areas where many people live together for the first time, such as army barracks during mobilization, university and college campuses[2] and the annual Hajj pilgrimage.[64] Although the pattern of epidemic cycles in Africa is not well understood, several factors have been associated with the development of epidemics in the meningitis belt. They include: medical conditions (immunological susceptibility of the population), demographic conditions (travel and large population displacements), socioeconomic conditions (overcrowding and poor living conditions), climatic conditions (drought and dust storms), and concurrent infections (acute respiratory infections).[90]
There are significant differences in the local distribution of causes for bacterial meningitis. For instance, while N. meningitides groups B and C cause most disease episodes in Europe, group A is found in Asia and continues to predominate in Africa, where it causes most of the major epidemics in the meningitis belt, accounting for about 80% to 85% of documented meningococcal meningitis cases.[90]
History
Some suggest that
It appears that epidemic meningitis is a relatively recent phenomenon.[94] The first recorded major outbreak occurred in Geneva in 1805.[94][95] Several other epidemics in Europe and the United States were described shortly afterward, and the first report of an epidemic in Africa appeared in 1840. African epidemics became much more common in the 20th century, starting with a major epidemic sweeping Nigeria and Ghana in 1905–1908.[94]
The first report of bacterial infection underlying meningitis was by the Austrian bacteriologist Anton Weichselbaum, who in 1887 described the meningococcus.[96] Mortality from meningitis was very high (over 90%) in early reports. In 1906, antiserum was produced in horses; this was developed further by the American scientist Simon Flexner and markedly decreased mortality from meningococcal disease.[97][98] In 1944, penicillin was first reported to be effective in meningitis.[99] The introduction in the late 20th century of Haemophilus vaccines led to a marked fall in cases of meningitis associated with this pathogen,[60] and in 2002, evidence emerged that treatment with steroids could improve the prognosis of bacterial meningitis.[75][78][98]
References
- ^ a b c d e f g h i j "Bacterial Meningitis". U.S. Centers for Disease Control and Prevention (CDC). 1 April 2014. Archived from the original on 5 March 2016. Retrieved 5 March 2016.
- ^ S2CID 6226323.
- ^ PMID 16394301.
- ^ PMID 14978146.
- ISBN 978-0-323-07699-9.
- from the original on 2 April 2020. Retrieved 14 October 2017.
- ^ a b "Viral Meningitis". U.S. Centers for Disease Control and Prevention (CDC). 26 November 2014. Archived from the original on 4 March 2016. Retrieved 5 March 2016.
- ^ PMID 15494903.
- ^ a b c d "Global Disease Burden 2019". Archived from the original on 19 April 2022. Retrieved 26 April 2022.
- PMID 23958365.
- ^ "NHS medical conditions meningitis". National Health Service (NHS). 20 October 2017. Archived from the original on 26 April 2022. Retrieved 26 April 2022.
- ^ a b c "Meningitis". World Health Organization (WHO). Archived from the original on 10 January 2022. Retrieved 30 May 2023.
- ^ a b "Meningococcal meningitis Fact sheet N°141". World Health Organization (WHO). November 2015. Archived from the original on 5 March 2016. Retrieved 5 March 2016.
- ISBN 978-0-323-06604-4. Archivedfrom the original on 10 September 2017.
- ^ Liddell HG, Scott R (1940). "μῆνιγξ". A Greek-English Lexicon. Oxford: Clarendon Press. Archived from the original on 8 November 2013.
- ^ (PDF) from the original on 3 August 2020. Retrieved 30 December 2018.
- ^ PMID 10411200.
- ^ PMID 18556318.
- ISBN 978-1-905813-31-5. Archived(PDF) from the original on 9 July 2014.
- S2CID 3196834.
- ^ "Meningitis". World Health Organization (WHO). Archived from the original on 25 April 2022. Retrieved 25 April 2022.
- ^ PMID 18174598.
- PMID 9696186.
- ^ a b "Amebic Meningitis". U.S. Centers for Disease Control and Prevention (CDC). 12 August 2022. Archived from the original on 24 May 2023. Retrieved 31 May 2023.
- ^ "Bacterial Meningitis". U.S. Centers for Disease Control and Prevention (CDC). 6 August 2019. Archived from the original on 5 March 2016. Retrieved 3 December 2020.
- ^ "Prevent Listeria". U.S. Centers for Disease Control and Prevention (CDC). 17 June 2019. Archived from the original on 7 May 2020. Retrieved 3 December 2020.
- ^ "Listeria (Listeriosis)". U.S. Centers for Disease Control and Prevention (CDC). 22 October 2015. Archived from the original on 19 December 2015. Retrieved 23 December 2015.
- PMID 19144940.
- PMID 18171202.
- PMID 11462183.
- ^ PMID 10675209.
- ^ PMID 18625686.
- ^ "Meningitis | Viral". U.S. Centers for Disease Control and Prevention (CDC). 19 February 2019. Archived from the original on 4 March 2016. Retrieved 26 March 2019.
- PMID 17029141.
- PMID 20673817.
- ^ ISBN 978-0-7817-6947-1. Archivedfrom the original on 15 May 2016.
- PMID 19665086.
- PMID 23083312.
- ISBN 978-1-4419-6639-1. Archivedfrom the original on 10 May 2016.
- PMID 23466647.
- ISBN 978-1-4419-6639-1. Archivedfrom the original on 16 May 2016.
- ^ S2CID 5735550.
- ^ PMID 19366917.
- S2CID 21335554.
- PMID 10371226.
- ISBN 978-0-19-856663-2.
- ^ from the original on 21 October 2020. Retrieved 18 October 2020.
- ^ S2CID 12415715.
- ^ PMID 12634067. Archived from the original (PDF) on 25 July 2011. – formal guideline at "Early management of suspected meningitis and meningococcal septicaemia in immunocompetent adults". British Infection Society. December 2004. Archivedfrom the original on 19 October 2013. Retrieved 19 October 2008.
- ^ PMID 32524581.
- ^ (PDF) from the original on 4 August 2020. Retrieved 30 December 2018.
Careful management of fluid and electrolyte balance is also important in the treatment of meningitis... there are different opinions regarding the cause of hyponatraemia... if dehydration, rather than inappropriately increased antidiuresis... fluid restriction is open to question
- ^ PMID 17062865.
- ^ from the original on 9 January 2012.
- S2CID 206172763.
- ^ PMID 15838017.
- PMID 30045416. CD005647.
- ISBN 978-0-19-852787-9.
- ^ a b c "Causes and How It Spreads". U.S. Centers for Disease Control and Prevention (CDC). 7 February 2022. Archived from the original on 29 June 2011. Retrieved 18 June 2011.
- ^ PMID 15802609.
- ^ PMID 10756001.
- ^ PMID 16418528.
- ^ a b "A new MenB (meningococcal B) vaccine". Meningitis Research Foundation. Archived from the original on 29 November 2014. Retrieved 23 November 2014.
- ^ a b "First vaccine approved by FDA to prevent serogroup B Meningococcal disease" (Press release). U.S. Food and Drug Administration (FDA). 29 October 2014. Archived from the original on 16 November 2014.
- ^ S2CID 9411482.
- PMID 11045076.
- PMID 21653957.
- PMID 19477559.
- ^ S2CID 19318114.
- ^ PMID 24163051.
- ^ PMID 25918919.
- (PDF) from the original on 4 August 2020. Retrieved 30 December 2018.
- PMID 29405037.
- PMID 17943757.
- PMID 27813057.
- ^ PMID 26362566.
- ^ PMID 19411436.
- PMID 27121755.
- ^ from the original on 29 August 2021. Retrieved 20 October 2018.
- PMID 9302246.
- ^ PMID 34813078.
- ^ "Meningitis and Encephalitis Fact Sheet". National Institute of Neurological Disorders and Stroke (NINDS). 11 December 2007. Archived from the original on 4 January 2014. Retrieved 27 April 2009.
- S2CID 37046726.
- ^ "Mortality and Burden of Disease Estimates for WHO Member States in 2002" (xls). World Health Organization (WHO). 2002. Archived from the original on 16 January 2013.
- PMID 9068303.
- PMID 25108337.
- PMID 25530442.
- from the original on 19 May 2020. Retrieved 23 March 2020.
- PMID 14259333.
- PMID 10674069.
- ^ a b c World Health Organization (1998). Control of epidemic meningococcal disease, practical guidelines, 2nd edition, WHO/EMC/BA/98 (PDF). Vol. 3. pp. 1–83. Archived (PDF) from the original on 30 October 2013.
- PMID 14509123.
- ^ ISBN 978-1-879284-62-3. Archivedfrom the original on 4 March 2022. Retrieved 24 August 2020.
- ^ Whytt R (1768). Observations on the Dropsy in the Brain. Edinburgh: J. Balfour.
- ^ S2CID 28838510.
- ^ Vieusseux G (1806). "Mémoire sur le Maladie qui a regne à Génève au printemps de 1805". Journal de Médecine, de Chirurgie et de Pharmacologie (Bruxelles) (in French). 11: 50–53.
- ^ Weichselbaum A (1887). "Ueber die Aetiologie der akuten Meningitis cerebro-spinalis". Fortschrift der Medizin (in German). 5: 573–83.
- PMID 19867668.
- ^ PMID 15509815.
- PMID 6366279.
External links
- Meningitis at Curlie
- Meningitis U.S. Centers for Disease Control and Prevention (CDC)