In 2019, meningitis was diagnosed in about 7.7 million people worldwide,[9] of whom 236,000 died, down from 433,000 deaths in 1990.[9] With appropriate treatment, the risk of death in bacterial meningitis is less than 15%.[1] Outbreaks of bacterial meningitis occur between December and June each year in an area ofsub-Saharan Africa known as themeningitis belt.[13] Smaller outbreaks may also occur in other areas of the world.[13] The wordmeningitis comes from theGreekμῆνιγξmeninx, 'membrane', and the medical suffix-itis, 'inflammation'.[14][15]
Neck stiffness, Texas meningitis epidemic of 1911–12
In adults, the most common symptom of meningitis is a severeheadache, occurring in almost 90% of cases of bacterial meningitis, followed by neck stiffness (the inability to flex the neck forward passively due to increased neckmuscle tone and stiffness).[16] The classic triad of diagnostic signs consists of neck stiffness, suddenhigh fever, andaltered 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 includephotophobia (intolerance to bright light) andphonophobia (intolerance to loud noises). Small children often do not exhibit the aforementioned symptoms, and may only beirritable and look unwell.[2] Thefontanelle (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 abnormalskin color.[18][19]
Neck stiffness occurs in 70% of bacterial meningitis in adults.[17] Other signs include the presence of positiveKernig's sign orBrudziński sign. Kernig's sign is assessed with the person lyingsupine, with the hip and knee flexed to 90 degrees. In a person with a positive Kernig's sign, pain limits passive extension of the knee. A positive Brudzinski's sign occurs when flexion of the neck causes involuntary flexion of the knee and hip. Although Kernig's sign and Brudzinski's sign are both commonly used to screen for meningitis, thesensitivity of these tests is limited.[17][20] They do, however, have excellentspecificity for meningitis: the signs rarely occur in other diseases.[17] Another test, known as the "jolt accentuation maneuver" (aka the "jolt test") helps determine whether meningitis is present in those reporting fever and headache. A person is asked to rapidly rotate the head horizontally; if this does not make the headache worse, meningitis is unlikely.[17]
Other problems can produce symptoms similar to those above, but from non-meningitic causes. This is calledmeningism or pseudomeningitis.[21]
Meningitis caused by the bacteriumNeisseria meningitidis (known as "meningococcal meningitis") can be differentiated from meningitis with other causes by a rapidly spreadingpetechial rash, which may precede other symptoms.[18] The rash consists of numerous small, irregular purple or red spots ("petechiae") on the trunk,lower extremities, mucous membranes, conjunctiva, and (occasionally) the palms of the hands or soles of the feet. The rash is typicallynon-blanching; the redness does not disappear when pressed with a finger or a glass tumbler. Although this rash is not necessarily present in meningococcal meningitis, it is relatively specific for the disease; it does, however, occasionally occur in meningitis due to other bacteria.[2] Other clues on the cause of meningitis may be the skin signs ofhand, foot and mouth disease andgenital herpes, both of which are associated with various forms of viral meningitis.[22]
Charlotte Cleverley-Bisman developed severe meningococcal meningitis as a young child; in her case, the petechial rash progressed togangrene and requiredamputation of all limbs. She survived the disease and became aposter child for a meningitis vaccination campaign inNew Zealand.
Thebrain tissue may swell,pressure inside the skull may increase, and the swollen brain mayherniate through the skull base. This may be noticed by a decreasinglevel of consciousness, loss of thepupillary light reflex, andabnormal posturing.[3] The inflammation of the brain tissue may also obstruct the normal flow of CSF around the brain (hydrocephalus).[3]Seizures may occur for various reasons; in children, seizures are common in the early stages of meningitis (in 30% of cases) and do not necessarily indicate an underlying cause.[8] Seizures may result from increased pressure and from areas of inflammation in the brain tissue.[3]Focal seizures (seizures that involve one limb or part of the body), persistent seizures, late-onset seizures and those that are difficult to control with medication indicate a poorer long-term outcome.[2]
Inflammation of the meninges may lead to abnormalities of thecranial nerves, a group of nerves arising from thebrain stem that supply the head and neck area and which control, among other functions, eye movement, facial muscles, and hearing.[2][17] Visual symptoms andhearing loss may persist after an episode of meningitis.[2] Inflammation of the brain (encephalitis) or itsblood vessels (cerebral vasculitis), as well as the formation ofblood clots in the veins (cerebral venous thrombosis), may all lead to weakness, loss of sensation, or abnormal movement or function of the part of the body supplied by the affected area of the brain.[2][3]
Meningitis is typically caused by aninfection. Most infections are due toviruses, and others due tobacteria,fungi, andparasites.[12] Mostly the parasites areparasitic worms,[4] but can also rarely includeparasiticamoebae.[24] Meningitis may also result from various non-infectious causes.[4] The termaseptic meningitis refers to cases of meningitis in which no bacterial infection can be demonstrated. This type of meningitis is usually caused by viruses, but it may be due to bacterial infection that has already been partially treated, when bacteria disappear from the meninges, or when pathogens infect a space adjacent to the meninges (such assinusitis).Endocarditis (an infection of theheart valves which spreads small clusters of bacteria through the bloodstream) may cause aseptic meningitis. Aseptic meningitis may also result from infection withspirochetes, a group of bacteria that includesTreponema pallidum (the cause ofsyphilis) andBorrelia burgdorferi (known for causingLyme disease), and may also result fromcerebral malaria (malaria infecting the brain).[4]
In adults,Neisseria meningitidis andStreptococcus pneumoniae together cause 80% of bacterial meningitis cases. The risk of infection withListeria monocytogenes is increased in people over 50 years old.[3][8] The introduction of the pneumococcal vaccine has lowered rates of pneumococcal meningitis in both children and adults.[28]
Ahead injury potentially allows nasal cavity bacteria to enter the meningeal space. Similarly, devices in the brain and meninges, such ascerebral shunts,extraventricular drains, orOmmaya reservoirs, carry an increased risk of meningitis. In these cases, people are more likely to be infected withStaphylococci,Pseudomonas, and otherGram-negative bacteria.[8] These pathogens are also associated with meningitis in people withan impaired immune system.[2] An infection in the head and neck area, such asotitis media ormastoiditis, can lead to meningitis in a small proportion of people.[8] Recipients ofcochlear implants for hearing loss are more at risk for pneumococcal meningitis.[29] In rare cases,Enterococcus spp. can be responsible for meningitis, both community and hospital-acquired, usually as a secondary result of trauma or surgery, or due to intestinal diseases (e.g.,strongyloidiasis).[30]
Recurrent bacterial meningitis may be caused by persisting anatomical defects, eithercongenital or acquired, or by disorders of theimmune system.[32] Anatomical defects allow continuity between the external environment and thenervous system. The most common cause of recurrent meningitis is askull fracture,[32] particularly fractures that affect the base of the skull or extend towards thesinuses andpetrous pyramids.[32] Approximately 59% of recurrent meningitis cases are due to such anatomical abnormalities, 36% are due to immune deficiencies (such ascomplement deficiency, which predisposes especially to recurrent meningococcal meningitis), and 5% are due to ongoing infections in areas adjacent to the meninges.[32]
The meninges comprise three membranes that, together with thecerebrospinal fluid, enclose and protect thebrain andspinal cord (thecentral nervous system). Thepia mater is a delicate impermeable membrane that firmly adheres to the surface of the brain, following all the minor contours. Thearachnoid mater (so named because of its spider-web-like appearance) is a loosely fitting sac on top of the pia mater. Thesubarachnoid space separates the arachnoid and pia mater membranes and is filled with cerebrospinal fluid. The outermost membrane, thedura mater, is a thick, durable membrane that is attached to both the arachnoid membrane and the skull.
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 onmucosal surfaces such as thenasal cavity. This is often in turn preceded by viral infections, which break down the normal barrier provided by the mucosal surfaces. Once bacteria have entered the bloodstream, they enter thesubarachnoid space in places where theblood–brain barrier is vulnerable – such as thechoroid plexus. Meningitis occurs in 25% of newborns with bloodstream infections due togroup B streptococci; this phenomenon is much less common in adults.[2] Direct contamination of the cerebrospinal fluid may arise from indwelling devices, skull fractures, or infections of the nasopharynx or the nasal sinuses that have formed a tract with the subarachnoid space (see above); occasionally,congenital defects of thedura mater can be identified.[2]
The large-scaleinflammation 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 theimmune system to the entry of bacteria into thecentral nervous system. When components of the bacterialcell membrane are identified by the immune cells of the brain (astrocytes andmicroglia), they respond by releasing large amounts ofcytokines, 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 ofwhite 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 increasedintracranial pressure; together with the lowered blood pressure often encountered insepsis, this means that it is harder for blood to enter the brain; consequentlybrain cells are deprived of oxygen and undergoapoptosis (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 ofcorticosteroids, are aimed at dampening the immune system's response to this phenomenon.[2][3]
Diagnosing meningitis as promptly as possible can improve outcomes.[47] There are nospecific signs or symptoms that can indicate meningitis, and alumbar puncture (spinal tap) to examine the cerebrospinal fluid is recommended for diagnosis.[47] Lumbar puncture is contraindicated if there is a mass in the brain (tumor or abscess) or theintracranial pressure (ICP) is elevated, as it may lead tobrain herniation. If someone is at risk for either a mass or raised ICP (recent head injury, a known immune system problem, localizing neurological signs, or evidence on examination of a raised ICP), aCT orMRI scan is recommended prior to the lumbar puncture.[8][48][49] This applies in 45% of all adult cases.[3]
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 asblood 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]
Cloudy CSF from a person with meningitis due to StreptococcusGram stain of meningococci from a culture showing Gram-negative (pink) bacteria, often in pairs
A lumbar puncture is done by positioning the person, usually lying on the side, applyinglocal anesthetic, and inserting a needle into thedural sac (a sac around the spinal cord) to collect cerebrospinal fluid (CSF). When this has been achieved, the "opening pressure" of the CSF is measured using amanometer. The pressure is normally between 6 and 18 cm water (cmH2O);[52] in bacterial meningitis the pressure is usually elevated.[8][48] Incryptococcal meningitis, intracranial pressure is markedly elevated.[53] The initial appearance of the fluid may prove an indication of the nature of the infection: cloudy CSF indicates higher levels of protein, white and red blood cells and/or bacteria, and therefore may suggest bacterial meningitis.[8]
The CSF sample is examined for presence and types ofwhite blood cells,red blood cells,protein content andglucose level.[8]Gram staining of the sample may demonstrate bacteria in bacterial meningitis, but absence of bacteria does not exclude bacterial meningitis as they are only seen in 60% of cases; this figure is reduced by a further 20% if antibiotics were administered before the sample was taken. Gram staining is also less reliable in particular infections such aslisteriosis.Microbiological culture of the sample is more sensitive (it identifies the organism in 70–85% of cases), but results can take up to 48 hours to become available.[8] The type of white blood cell predominantly present (see table) indicates whether meningitis is bacterial (usually neutrophil-predominant) or viral (usually lymphocyte-predominant),[8] although at the beginning of the disease, this is not always a reliable indicator. Less commonly,eosinophils predominate, suggesting parasitic or fungal etiology, among others.[43]
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 theblood glucose (CSF glucose to serum glucose ratio). A ratio ≤0.4 is indicative of bacterial meningitis;[52] in the newborn, glucose levels in CSF are normally higher, and a ratio below 0.6 (60%) is therefore considered abnormal.[8] High levels oflactate in CSF indicate a higher likelihood of bacterial meningitis, as does a higher white blood cell count.[52] If lactate levels are less than 35 mg/dl and the person has not previously received antibiotics, then this may rule out bacterial meningitis.[54]
Various other specialized tests may be used to distinguish between different types of meningitis. Alatex agglutination test may be positive in meningitis caused byStreptococcus pneumoniae,Neisseria meningitidis,Haemophilus influenzae,Escherichia coli andgroup B streptococci; its routine use is not encouraged as it rarely leads to changes in treatment, but it may be used if other tests are not diagnostic. Similarly, thelimulus lysate test may be positive in meningitis caused by Gram-negative bacteria, but it is of limited use unless other tests have been unhelpful.[8]Polymerase chain reaction (PCR) is a technique used to amplify small traces of bacterial DNA to detect the presence of bacterial or viral DNA in cerebrospinal fluid; it is a highly sensitive and specific test since only trace amounts of the infecting agent's DNA is required. It may identify bacteria in bacterial meningitis and may assist in distinguishing the various causes of viral meningitis (enterovirus,herpes simplex virus 2, andmumps in those not vaccinated for this).[22]Serology (identification of antibodies to viruses) may be useful in viral meningitis.[22] If tuberculous meningitis is suspected, the sample is processed forZiehl–Neelsen stain, which has a low sensitivity, and tuberculosis culture, which takes a long time to process; PCR is being used increasingly.[31] Diagnosis of cryptococcal meningitis can be made at low cost using anIndia ink stain of the CSF; however, testing for cryptococcal antigen in blood or CSF is more sensitive.[55][56]
A diagnostic and therapeutic difficulty is "partially treated meningitis", where there are meningitis symptoms after receiving antibiotics (such as for presumptivesinusitis). 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]
Histopathology of bacterial meningitis: autopsy case of a person with pneumococcal meningitis showing inflammatory infiltrates of thepia mater consisting of neutrophil granulocytes (inset, higher magnification).
Meningitis can be diagnosed after death has occurred. The findings from apost mortem are usually a widespread inflammation of thepia mater andarachnoid layers of the meninges.Neutrophil granulocytes tend to have migrated to the cerebrospinal fluid and the base of the brain, along withcranial nerves and thespinal cord, may be surrounded withpus – as may the meningeal vessels.[57]
For some causes of meningitis, protection can be provided in the long term throughvaccination, or in the short term withantibiotics. Some behavioral measures may also be effective.
Bacterial and viral meningitis are contagious, but neither is as contagious as thecommon cold orflu.[58] Both can be transmitted through droplets of respiratory secretions during close contact such as kissing, sneezing or coughing on someone,[58] but bacterial meningitis cannot be spread by only breathing the air where a person with meningitis has been. Viral meningitis is typically caused byenteroviruses, and is most commonly spread through fecal contamination.[58] The risk of infection can be decreased by changing the behavior that led to transmission.
Since the 1980s, many countries have includedimmunization againstHaemophilus influenzae type B in their routine childhood vaccination schemes. This has practicallyeliminated 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 before 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 inHajj.[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 weakresponse from the immune system, or cross-react with normal human proteins.[59][61] Still, some countries (New Zealand,Cuba,Norway andChile) 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 population at risk with bivalent A/C or trivalent A/C/W135 polysaccharide vaccines,[65] though the introduction ofMenAfriVac (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 againstStreptococcus pneumoniae with thepneumococcal conjugate vaccine (PCV), which is active against seven common serotypes of this pathogen, significantly reduces the incidence of pneumococcal meningitis.[59][68] Thepneumococcal polysaccharide vaccine, which covers 23 strains, is only administered to certain groups (e.g. those who have had asplenectomy, the surgical removal of the spleen); it does not elicit a significant immune response in all recipients, e.g. small children.[68] Childhood vaccination withBacillus Calmette-Guérin has been reported to significantly reduce the rate of tuberculous meningitis, but its waning effectiveness in adulthood has prompted a search for a better vaccine.[59]
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 orceftriaxone) 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 abasilar 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]
Meningitis is potentially life-threatening and has a high mortality rate if untreated;[8] delay in treatment has been associated with a poorer outcome.[3] Thus, treatment with wide-spectrum antibiotics should not be delayed while confirmatory tests are being conducted.[49] If meningococcal disease is suspected in primary care, guidelines recommend thatbenzylpenicillin be administered before transfer to hospital.[18]Intravenous fluids should be administered ifhypotension (low blood pressure) orshock are present.[49] It is not clear whether intravenous fluid should be given routinely or whether this should be restricted.[71] Given that meningitis can cause many early severe complications, regular medical review is recommended to identify these complications early[49] and to admit the person to anintensive care unit, if deemed necessary.[3]
Mechanical ventilation may be needed if the level of consciousness is very low or if there is evidence ofrespiratory failure. If there are signs of raised intracranial pressure, measures to monitor the pressure may be taken; this would allow the optimization of thecerebral perfusion pressure and various treatments to decrease the intracranial pressure with medication (e.g.,mannitol).[3] Seizures are treated withanticonvulsants.[3] Hydrocephalus (obstructed flow of CSF) may require insertion of a temporary or long-term drainage device, such as acerebral shunt.[3] The osmotic therapy,glycerol, has an unclear effect on mortality but may decrease hearing problems.[72]
Structural formula of ceftriaxone, one of the third-generation cefalosporin antibiotics recommended for the initial treatment of bacterial meningitis.
Empiric antibiotics (treatment without exact diagnosis) should be started immediately, even before the results of the lumbar puncture and CSF analysis are known. The choice of initial treatment depends largely on the kind of bacteria that cause meningitis in a particular place and population. For instance, in the United Kingdom, empirical treatment consists of a third-generationcefalosporin such ascefotaxime orceftriaxone.[48][49] In the US, where resistance to cefalosporins is increasingly found in streptococci, addition ofvancomycin to the initial treatment is recommended.[3][8][48]Chloramphenicol, either alone or in combination withampicillin, however, appears to work equally well.[73]
Empirical therapy may be chosen based on the person's age, whether the infection was preceded by ahead injury, whether the person has undergone recentneurosurgery, 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 ofampicillin is recommended to coverListeria 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 CSFculture 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 inclinical trials. Rather, the relevant knowledge has mostly derived from laboratory studies inrabbits.[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]
Fluids given intravenously are an essential part of the treatment of bacterial meningitis. There is no difference in terms of mortality or acute severe neurological complications in children given a maintenance regimen over a restricted-fluid regimen, but evidence is in favor of the maintenance regimen in terms of the emergence of chronic severe neurological complications.[74]
Additional treatment withcorticosteroids (usuallydexamethasone) has shown some benefits, such as a reduction ofhearing loss, and better short term neurological outcomes[75] in adolescents and adults fromhigh-income countries with low rates of HIV.[76] Some research has found reduced rates of death[76] while other research has not.[75] They also appear to be beneficial in those with tuberculosis meningitis, at least in those who are HIV negative.[77]
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 has 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 fromlow-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 before the first dose of antibiotics, and is greatest in cases ofH. influenzae meningitis,[8][79] the incidence of which has decreased dramatically since the introduction of theHib vaccine. Thus, corticosteroids are recommended in the treatment of pediatric meningitis if the cause isH. influenzae, and only if given before the first dose of antibiotics; other uses are controversial.[8]
In addition to the primary therapies 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 consequences. Examples of adjuvant therapies that have been trialed includeacetaminophen,immunoglobulin therapy,heparin,pentoxifyline, and a mononucleotide mixture withsuccinic 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 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 andvaricella zoster virus may respond to treatment with antiviral drugs such asaciclovir, 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, such ascryptococcal meningitis, is treated with long courses of high doseantifungals, such asamphotericin B andflucytosine.[55][82] Raised intracranial pressure is common in fungal meningitis, and frequent (ideally daily) lumbar punctures to relieve the pressure are recommended,[55] or a lumbar drain.[53]
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 byH. influenzae and meningococci has a better prognosis than cases caused by group B streptococci, coliforms andS. 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, includingsensorineural hearing loss,epilepsy,learning, and behavioral difficulties, as well asdecreased 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 aredeafness (in 14%) andcognitive 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 survive with no problems.[85]
Although meningitis is anotifiable disease in many countries, the exactincidence rate is unknown.[22] In 2013, meningitis resulted in 303,000 deaths, down from 464,000 deaths in 1990.[86] In 2010 it was estimated that meningitis resulted in 420,000 deaths,[87] excludingcryptococcal meningitis.[42]
Bacterial meningitis occurs in about 3 people per 100,000 annually inWestern 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 bymedical 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 annualHajj 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, whileN. 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]
Some suggest thatHippocrates may have realized the existence of meningitis,[17] and it seems thatmeningism was known to pre-Renaissance physicians such asAvicenna.[92] The description of tuberculous meningitis, then called "dropsy in the brain", is often attributed to Edinburgh physicianSir Robert Whytt in a posthumous report that appeared in 1768, although the link with tuberculosis and its pathogen was not made until the next century.[92][93]
It appears that epidemic meningitis is a relatively recent phenomenon.[94] The first recorded major outbreak occurred inGeneva 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 sweepingNigeria andGhana in 1905–1908.[94]
The first report of bacterial infection underlying meningitis was by the Austrian bacteriologistAnton Weichselbaum, who in 1887 described themeningococcus.[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 scientistSimon 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 ofHaemophilus 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]
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