Meningitis and Encephalitis

Viral Meningitis

This is the most common cause of meningitis and tends to be less serious than the bacterial form and is rarely life threatening. In addition, viral meningitis cannot cause blood poisoning (septicaemia) which is usually life threating if left untreated. It commonly affects children under the age of 5 and those with a weak immune system. In the UK, viral meningitis is more widespread during the summer and autumn months. It is not known how many people get viral meningitis each year in the UK as most cases are mild and not reported. However it is estimated that there are many thousands of cases each year.

Viruses that can cause meningitis are:

• Enteroviruses (viruses that live in your intestine)
• Herpes Simplex Virus
• Mumps and Measles virus
• Epstein Barr virus
• Human immunodeficiency virus (HIV)
• Cytomegalovirus (CMV)

Bacterial Meningitis

Bacterial meningitis, as its name suggests, is caused by different types of bacteria. Some of the bacteria that can cause meningitis are naturally carried by many people and do not cause them any issues. For example many people carry these bacteria harmlessly at the back of their nose and throat as well as in other areas of the body. In some cases however the bacteria manage to penetrate into the blood stream where they can cause disease. Any condition that facilitates the penetration of the bacteria into the blood stream can increase the risk of meningitis. Therefore the elderly and those with weakened immune systems can be at risk including young children whose immune systems have not fully developed as yet. In addition, in very young babies the bacteria can be passed inadvertently from mother to the child.

In children and young people aged 3 months or older, the most frequent causes of bacterial meningitis include Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae type b (Hib). In neonates (children younger than 28 days), the most common causative organisms are Streptococcus agalactiae (Group B streptococcus), Escherichia coli, S pneumoniae and Listeria monocytogenes.

Bacterial meningitis is a medical emergency. Cases can arise suddenly, with symptoms worsening within hours to a couple of days and so it is usually acute. Rapid identification and treatment is crucial. The bacteria that cause bacterial meningitis can also spill into the blood and then multiply causing septicaemia (blood poisoning). If this occurs, organs such as the kidneys and liver can be affected and it can also cause damage to the limbs. Therefore, untreated bacterial meningitis is usually fatal. However, bacterial meningitis can also be caused by septicaemia where the bacteria in the blood stream enter the brain and cause it to be infected. Therefore meningitis can occur with or without septicaemia. Meningococcal disease most commonly presents as bacterial meningitis (15% of cases) or septicaemia (25% of cases), or as a combination of the two syndromes (60% of cases).

Children under the age of 4 seem to be at most risk of bacterial meningitis as well as teenagers aged 15-19 years of age. The overall annual incidence of acute bacterial meningitis in the UK is 1 per 100,000 population. The most common bacteria that cause bacterial meningitis are:

• Neisseria meningitidis – called meningococcal meningitis. This is the most common form in the UK and it is highly contagious. There are several different strains of meningococcal bacteria that cause disease. The most common disease causing groups in the UK are meningococcal A, B, C, W and Y. These are commonly referred to as MenA, MenB, MenC, MenW and MenY. The majority of cases in the UK are caused by strain B. Strain C used to be common, but vaccination introduced in 1999 now prevents most of these cases. Since 2009, cases of MenW disease have been on the increase in the UK. Meningococcal bacteria are common. It is estimated that about 10% of the population carry them in the back of the nose or throat. Carriage is less common in young children than in adults. Young adults have the highest rate of carriage, with up to one in four harbouring the bacteria. As well as infecting the meninges, meningococcal bacteria can also cause septicaemia. This may be called meningococcal septicaemia. It is commonly seen in college/university students, infants, children, international travellers, and the immunocompromised.
• Streptococcus pneumoniae – called pneumococcal meningitis. This is the second most common cause of bacterial meningitis in the UK. According to a study in 2005, approximately half of pre-school children carry pneumococcal bacteria in the back of their nose and throat. These bacteria are therefore passed around by coughing, sneezing and close contact. In most cases carrying these bacteria is harmless. However in susceptible people these bacteria can cause a variety of illnesses including minor illness such as ear and sinus infections as well as life threating illnesses such as pneumonia and meningitis. Occasionally, pneumococcal meningitis can develop from a milder form of the infection such as earache. Infants under 2 years old and those with compromised immune systems are at greatest risk for it. A pneumococcal vaccine which protects against 13 strains of the bacteria is now given as part of the routine immunisation programme in the UK. It protects against some forms of pneumococcal meningitis but not all. Pneumococcal meningitis can result in septicaemia but not as often as in meningococcal meningitis. Most cases of pneumococcal meningitis are in children under two years old,
• Adults over the age of 65 and in those with medical problems that put them at increased risk of disease. Pneumococcal meningitis can be severe and has a higher risk of death and long term brain damage than most other causes of bacterial meningitis. Haemophilus influenzae type b – once the most common cause of bacterial meningitis, its incidence has decreased because of widespread vaccination of children. Since the Hib vaccine was introduced in the UK in 1992, cases have dropped by over 90%. It mainly affects children under 4 years of age.. In the UK, cases in adults tend to occur in people who are likely to mix with children, such as parents and grandparents
• Group B streptococcus- Streptococcus agalactiae is a type of Group B streptococcus most often responsible for meningitis. It is the biggest cause of meningitis in neonates. The bacteria normally live in the bowels and the vagina and sometimes in the back of the nose and throat. The bacteria can be transmitted from mother to baby before or during birth. A study, supported by Meningitis Research Foundation, found that the incidence of Group B streptococcal infection in newborns in the UK and Ireland is around 7 cases per 10 000 live births.
• Escherichia coli, and Listeria monocytogenes are the most common causes of meningitis in the neonate (babies less six weeks old) and may be passed from the mother to her baby. Listeria meningitis can also affect the elderly and those with a weakened immune system. Very few cases now occur each year in the UK and Ireland, largely due to successful education campaigns about the dangers of eating unpasteurised milk products or contaminated pate, poultry or shellfish in pregnancy. E coli meningitis most commonly occurs in newborn babies or babies under 3 months of age. In the UK and Ireland adults and older children almost never get E coli meningitis unless they have health problems that suppress their immune system, or have had head injuries or surgery to the head so that bacteria can enter via the head wound.
• Group A streptococcus -commonly found on the surface of the skin and in the throat. These bacteria commonly cause mild throat, skin, ear and sinus infections in both adults and children. More rarely these bacteria cause an invasive infection where they penetrate deeper into the tissues and organs of the body causing more serious disease. If they penetrate into the tissues of the brain this may result in meningitis. Whilst mild illnesses caused by GAS are quite common, invasive infection is much rarer affecting approximately 3 people per in 100,000 in the UK
• Salmonella– this is a very rare form of meningitis caused by salmonella bacteria. It usually affects newborn babies, but cases may also occur in immunodeficient adults. In a few rare cases, an unusual form of salmonella meningitis has been transmitted to babies, pregnant women and immunodeficient adults by pet reptiles. This is more widely known in the US where pet reptiles are more popular
• Tuberculosis – this is a rare form of meningitis. Diagnosis of TB meningitis can be difficult because the onset of illness is not as sudden as with other types of bacterial meningitis

Chronic Meningitis

Chronic meningitis is meningitis symptoms that last for more than 4 weeks. Again it can be caused by infections but other non-infective causes such as connective tissue disease and malignancy may also be the cause. In up to a third of cases no cause is found. The most common cause of chronic meningitis is Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB). This accounts for 40–60% of cases. However, other bacterial causes include Treponema pallidum which causes syphilis. Meningococcal bacteria rarely cause chronic meningitis. Other infective causes include fungi and parasites. Fungal meningitis is most commonly seen in immunocompromised patients, such as those with HIV/AIDS, but it may affect anyone. The most common fungal cause is Cryptococcus neoformans (cryptococcal meningitis), which is found in dirt and bird droppings. Other fungal causes include Coccidioides immitis, Histoplasma capsulatum, and Candida species. Amoebic meningitis is rare and can be lethal. It is caused by the free-living amoeba, Naegleria fowleri, a single-cell parasite, which can be found in warm water lakes and rivers.

Meningitis may also be recurrent. There is a rare condition called Mollaret’s meningitis which is a recurrent form of meningitis. It is thought to be caused in many cases by an infection with a member of the herpes family of viruses. Patients with this condition usually experience viral meningitis more than once and are often given acyclovir to prevent recurrence if the cause turns out to be the herpes virus. Recurrent meningitis is more common in patients with immune deficiencies or underlying structural defects in the brain.

Encephalitis is an inflammation of the brain characterised by fever, headache, and an altered state of consciousness, with or without seizures. Encephalitis itself is not common however, and it is estimated that there are 4000 new cases of encephalitis in the UK every year. The symptoms may be very mild and in view of this there are probably many more cases with mild symptoms that occur but are not documented.

Viruses are the most common cause of encephalitis. However, other infectious organisms may be involved and it can also be caused by non-infectious causes such as by the autoimmune system attacking the brain. The herpes simplex virus is the most common cause of encephalitis in the UK. The herpes zoster virus that causes chickenpox is also common. Other common viruses involved are enterovirus, the mumps virus and the Epstein-barr virus. Rarely, other viruses may be involved such as the rabies virus (from an animal bite), or arboviruses. Arboviruses are usually spread by insects such as infected mosquitoes or ticks. Therefore, throughout the world where other insects may be more common, different types of arbovirus-related encephalitis may be seen.

In the United Kingdom (UK), the incidence of measles virus infections has gradually increased since 2006. The increased incidence of measles has meant that its complications such as encephalitis (inflammation and swelling of the brain) are also seen more frequently. Whilst measles encephalitis is uncommon, it can occur in various forms and can affect children at the time of the infection but also up to many years after. Measles encephalitis occurs in only around 0.05% - 0.1% of measles cases.

Mumps infection typically causes meningitis but can also cause encephalitis. Mumps encephalitis occurs in around 1 in 1000 people who develop viral meningitis from mumps. Complications from mumps are most likely to occur in adults rather than children.

Bacterial, fungal, and parasitic encephalitis are very rare. Bacterial meningoencephalitis may develop from the bacteria that cause meningitis. Tick-transmitted Lyme disease may cause bacterial encephalitis as can mycobacterium tuberculosis which causes TB. Toxoplasma gondii, a parasite associated with cats, can cause parasitic encephalitis in some people with compromised immune systems. Other bacteria, fungi, and parasites can occasionally cause encephalitis.

There are two types of encephalitis, primary and secondary. In primary encephalitis, the brain and spinal cord are infected directly. The infection may be limited to a single location (focal) or be spread throughout the brain (generalised). Secondary encephalitis, also known as post-infective encephalitis, can result from complications of a current or previous viral infection. In these cases the auto-immune system which normally fights off the virus can start attacking the brain. It can also be caused by the same reaction of the auto-immune system to a vaccination or a tumour. Post-infectious and autoimmune/inflammatory encephalomyelitis are broadly represented by the syndrome called acute disseminated encephalomyelitis (ADEM). In this syndrome the inflammation damages a special protective sheath around the nerve fibres called myelin. This damages the nerve fibres and can cause loss of function of certain parts of the body supplied by these nerves, in addition to the general features of headache and fever. ADEM is more common in children.

In addition, encephalitis can also be divided into acute and chronic. The acute form is more common. However, chronic encephalitis can occur where the inflammation occurs slowly over months. This can be caused by the HIV virus however it can be caused also be caused by other unknown causes.

Meningitis and encephalitis may start with flu-like symptoms and intensify over a few hours to a few days. Initial symptoms that can be common to both are:

• Fever ( usually >38°C)
• Headache
• Nausea and vomiting
• Joint pain

After this the symptoms usually become more typical for the individual disease. However, affected individuals may not have all of these symptoms and someone can still have either of the two diseases with very few symptoms. Common symptoms of meningitis include:

• neck stiffness
• sensitivity to bright lights
• confusion
• fits
• a rash
• severe arm or leg pain

As meningitis can also present with septicaemia there may be other features present.

The symptoms of septicaemia include:

• sudden onset of a high fever
• being sick
• pale or blotchy skin
• difficulty breathing
• shivering or having cold hands and feet
• aching limbs or joints
• a rash
• drowsiness, confusion or loss of consciousness

The typical septicaemic rash of meningitisis red/purple and doesn’t go away when the bottom of a glass is pressed onto it (the tumbler test). However, this is usually a late sign of meningitis and it is not always present. Other, non septicaemic rashes can be present in meningitis which may look different. In addition, the rash of viral meningitis may also look different to this. Therefore it is important to pay attention to any rash you see and report it to a doctor.

Encephalitis on the other hand usually presents with:

• headache
• fever
• altered consciousness

Encephalitis symptoms may also include neurological problems: difficulty with hearing or speech, involuntary eye movements, such as moving the eyes from side to side, loss of sensation, partial paralysis, seizures, hallucinations, muscle weakness, changes in personality, and coma. Other symptoms that overlap with meningitis may also occur such as sensitivity to bright light and a stiff neck.

It is also important to be aware that not all cases show all these classical signs. Elderly patients for example may be simply lethargic and show few other signs. Patients with compromised immune systems may have atypical symptoms and be harder to diagnose. Infants tend to have different symptoms to older children. As such they may be irritable and cry when they are held, vomit, be stiff or very floppy,, have seizures or jerky movements and refuse food. When examined they mayhave bulging fontanelles (the soft spots on the top of the head) and pale or blotchy skin.

As the early signs of meningitis or encephalitis may present very similarly to flu with non-specific symptoms such as fever and malaise it is important that early signs are reported to medical staff. This is particularly important as patients with meningitis can rapidly deteriorate.

Complications and Prognosis
The outcome of those with meningitis and encephalitis depends on the specific cause of the condition, the severity, the patient’s health and immune status, and how quickly the condition is identified and treated. Patients with mild cases may recover fully within a few weeks or may have persistent or permanent complications. In general cases that are diagnosed and treated quickly have a good prognosis. However, as many as 15-25% of newborns and 15% of other patients with bacterial meningitis die, even when treated appropriately and rapidly. Up to 15-25% of those who survive may have neurological problems including hydrocephalus, cerebral palsy, deafness, blindness, seizures, and/or some degree of impaired thinking. Other complications may include limb amputation, renal problems and bone and joint problems usually from complications of septicaemia. Viral meningitis seems to carry a better prognosis. However, mortality following HSV infection of the central nervous system is 15%. HSV-1 and HSV-2 have the same risk of mortality but HSV-2 is more often associated with long-term complications such as cerebral palsy, mental retardation, seizures, microcephaly (an abnormally small head) and visual impairment. These complications may occur at any age, but newborns are at the highest risk. With regards to encephalitis, overall about 10% of cases are fatal.

Doctors start with a physical examination and a medical history. This examination may occur in the accident and emergency centre (A and E) as symptoms may suddenly appear and rapidly worsen over several hours to a couple of days. Of interest to the doctor are recent illnesses, exposure to animals, mosquitoes, or ticks, contact with other people who have become ill, recent travel and recent activities. The doctor will note the presence or absence of signs and symptoms frequently associated with meningitis and encephalitis. Neurological examinations may be performed to assess the status of the patient’s nervous system, their sensory and motor function, coordination, vision, hearing, strength and thinking.

Laboratory Tests
Laboratory tests are performed to detect, identify, evaluate, and monitor meningitis and encephalitis. These tests are performed in order to:

• Distinguish these infectious diseases from other conditions with similar symptoms
• Determine the cause – bacterial, viral, fungal, parasitic, or other as rapidly as possible to start and guide treatment
• Evaluate the patient’s general state of health, immune system status, current signs and symptoms, and current complications to guide symptom relief and to minimize inflammation and neurological or brain damage
• Where possible, determine the infection’s source; especially important when the causative agent may be a public health concern

Tests include:
Cerebrospinal fluid (CSF) analysis. This is an important test for encephalitis and meningitis. CSF analysis is a group of common tests that can be requested and performed on a sample of CSF fluid. CSF is collected using a procedure called a lumbar puncture or spinal tap.

Initial CSF tests — The initial basic set of CSF tests that are often performed with suspected infections of the central nervous system include:

• Physical characteristics. Normal CSF appears clear and colourless. The appearance of the sample of CSF is usually compared to a sample of water. In infections, the initial pressure of CSF during collection may be increased, and the sample may appear cloudy due to the presence of white blood cells (WBCs) or microorganisms.
• CSF protein. Only a small amount is normally present in CSF because proteins are large molecules and do not cross the blood/brain barrier easily. Increases in protein are commonly seen with meningitis, brain abscesses, and neurosyphilis and their presence in large amounts indicates infection.
• CSF glucose. Normal levels are about 2/3 the concentration of the blood glucose concentration. Glucose levels may decrease when cells that are not normally present use up (metabolise) the glucose. These may include bacteria or cells present due to inflammation (WBCs). Therefore a low CSF glucose may indicate the presence of infection.
• CSF total cell counts. WBCs may be increased with central nervous system (CNS) infections.
• CSF WBC differential. Small numbers of lymphocytes, monocytes (and in neonates, neutrophils) are normal in a sample of CSF. There may be:
  • an increase in neutrophils with a bacterial infection
  • an increase in lymphocytes with a viral infection
  • sometimes an increase in eosinophils with a parasitic infection
• CSF Gram stain for direct observation of bacteria
• CSF culture and sensitivity to identify the presence of bacteria, fungi, and viruses and to determine what medications would be effective in destroying them.

Additional or follow-up CSF tests — If any of the initial tests are abnormal, then additional infectious testing may be requested. This may include one or more of the following:

• Detection of viruses by PCR (polymerase chain reaction) – this involves the detection of viral genetic material (DNA, RNA) such as herpes and enteroviruses using a special biochemical method
• CSF Cryptococcal antigen – to detect a specific fungal infection called Cryptococcus
• Other CSF antigen tests – depending on which organism(s) are suspected
• Specific CSF antibody tests – depending on which organism(s) are suspected

Less commonly requested CSF infectious diseases tests include:

• CSF AFB smear and culture (when tuberculosis is suspected) – positive with tuberculosis and with other mycobacteria
• CSF Molecular tests to detect Mycobacteria tuberculosis
• CSF syphilis testing (VDRL) – positive with neurosyphilis; a negative result however does not rule out the condition

Several other types of CSF testing may occasionally be requested to help distinguish between viral and bacterial meningitis:

• CSF lactic acid—may be used to distinguish between viral and bacterial meningitis. The level will usually be increased with bacterial and fungal meningitis while it will remain normal or only slightly elevated with viral meningitis.
• CSF lactate dehydrogenase (LDH) – is sometimes used to differentiate between bacterial and viral meningitis also.  The levels are usually a lot higher in bacterial meningitis.
• CSF C-reactive protein (CRP) is an acute phase reactant and is elevated with inflammation. It is markedly increased with bacterial meningitis. 

Laboratory tests on samples other than CSF—may be requested with or following CSF testing and may include:

• Blood glucose, protein, FBC (Full Blood Count) – to evaluate and to compare with CSF levels
• Tests for antibodies or antigens in the blood for a variety of viruses and bacteria e.g. syphilis, HIV. This can help identify if a patient is currently infected or has recently been infected with a microorganism that could potentially be the source of the meningitis or encephalitis.
• Blood cultures may be requested to detect and identify bacteria in the blood. This may be especially helpful if there is suspected septicaemia.
• Cultures of other parts of the body may be performed to detect the source of the infection that led to the meningitis or encephalitis e.g. urine.  A chest x-ray may also be performed for that same reason.
• U&Es, LFTs, CRP – tests that evaluate organ function.

Non-Laboratory Tests
Imaging tests may be performed to look for signs of brain inflammation or abnormalities but they may be normal with encephalitis. However, brain damage, tumours, bleeding, and abscesses may be detected. Tests may include:

• CT (Computed tomography) – this may also be used to diagnose raised intracranial pressure which is a contra-indication to a lumbar puncture.
• MRI (Magnetic Resonance Imaging) - this is more sensitive than a CT scan and can show up the inflammatory changes and any other complications.
• Ultrasound - this modality is usually used in infants
• EEG (Electroencephalography) – to detect abnormal brain waves

Vaccination remains the main stay of prevention of developing meningitis or encephalitis. However other methods to reduce your risk of exposure to the pathogens that can cause meningitis/encephalitis are also important. This means hand washing, avoiding contact with others who are unwell and in some cases avoiding certain uncooked foods to avoid exposure to bacteria such as listeria and salmonella. It is also important to remember that no vaccine is 100% effective and therefore there is still a chance vaccinated people can develop bacterial meningitis.

There are vaccines available for Haemophilus influenzae type b, some types of Streptococcus pneumoniae, and some types of Neisseria meningitides. These can all cause meningitis and the vaccines are part of the routine immunisation schedule for children. Widespread vaccination of children has drastically reduced the incidence of meningitis caused by Haemophilus influenzae type b as well as Meningitis Types B and C in the UK. As a result other vaccines targeting other strains of Neisseria meningitides have been developed.

Vaccinations against Neisseria Meningitides

The MenACWY vaccine was introduced in the UK in August 2015 to protect teenagers against a harmful strain of meningococcal W (MenW) disease which had been rapidly rising since 2009. MenACWY vaccine is offered to teenagers in school year 9. If you are over 14 and did not get this vaccine at school or from your GP you can still get the vaccine if you are starting university for the first time and aged under 25 or you were born after 1st September 1996 (England and Wales).

The MenB vaccine has been offered as part of the routine immunisation schedule for children since September 2015 in UK and babies born on or after 1 May were offered the vaccine as part of a one off catch-up campaign. The vaccine is also available free of charge to people in the UK and Ireland with medical conditions that increase their risk of the disease. They can also be purchased privately in the UK for those not eligible for free vaccination on the NHS.

The MenC vaccine is routinely given to children in the UK at 12-13 months of age with a booster dose for teenagers at 14 years. Due to vaccination we only see around 40 of cases of MenC each year.

Pneumococcal Vaccination

Infants are immunised against pneumococcus infections now at age 3 and 12 months usually with a vaccine called prevenar 13. This protects against 13 strains of pneumococcus. Vaccination with PCV13 not only provides direct protection to the person vaccinated but also stops them from carrying the bacteria in the back of the nose and throat, preventing them from passing it to others. This is very common in young children so helps prevent the risk of transmission from them to others.

HiB vaccination

Since the introduction of the Hib vaccine, the incidence of meningitis cause by Haemophilus influenzae has been reduced by over 90%, across the UK and Ireland. Currently in the UK, the vaccine is offered to babies at 2, 3, and 4 months of age in the routine immunisation programme, with a Hib booster (given as combined Hib/MenC) offered at 12-13 months of age. Older children and adults with certain immune deficiencies such as people with HIV or those without a functioning spleen, including people who have sickle cell disorder, are also eligible for the vaccine.

MMR Vaccination

Before the MMR vaccination was introduced in 1998 mumps was a leading cause of viral meningitis. Mumps was also the most frequent cause of viral encephalitis and measles encephalitis could develop in around 0.1% of those with measles. Vaccination with the MMR has reduced the incidence of both meningitis and encephalitis caused by measles and mumps.

Other vaccines

Other vaccines may be used for travellers going to meningitis-prone or encephalitis prone countries where arboviruses are more common. Vaccinations are available for Japanese encephalitis, tick-borne encephalitis and encephalitis caused by rabies. Arbovirus risk however can be minimised by limiting exposure to mosquitoes, limiting outdoor activities at night, wearing long sleeved clothing, using insect repellents, and eliminating freestanding water around the home.

Antibiotics

Those with close contact with someone who has had meningococcal meningitis may be prescribed antibiotics for a few days to decrease their risk of developing an infection. Close contacts usually means household members, or intimate kissing contacts within the previous week. These people are offered a short course of antibiotics to prevent possible infection although their risk is low. Household and kissing contacts of confirmed cases of Group A, C, W135 or Y meningococcal disease are usually also given meningococcal vaccine in addition to antibiotics. If there has been an outbreak of meningococcal infection antibiotics and/or immunisation may then be offered to a wider group of people e.g. students in the same class for example.