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REVIEW

Meningitis : Vaccines and


prophylaxis
Jacqui Souter, BPharm, Amayeza Info Centre

Abstract
Meningitis is an inflammatory disease of the meninges covering the brain. Bacteria, viruses, fungi,
chemicals or inflammatory conditions are some of the potential causes of meningitis. In this article, we
discuss prevention of the three most common bacterial causes of meningitis: Streptococcus pneumoniae,
Neisseria meningitidis and Haemophilus influenzae.

iral, bacterial and fungal infections are the most common


causes of meningitis. However, subarachnoid haemorrhage, chemicals, cancers and other inflammatory conditions
may also lead to meningitis.1
In this article we discuss bacterial meningitis with specific
emphasis on the most common causes of bacterial meningitis
occurring after the neonatal period, namely Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae.1
The brain and spinal cord are covered by membranes called
the meninges. The meninges are made up of three separate
membranes namely the dura mater, the arachnoid and the pia
mater. The dura mater is directly beneath and adheres to the
skull. The pia mater is the membrane that covers the brain and
the arachnoid is situated between the dura mater and the pia
mater. The region between the arachnoid and the pia mater is
where the cerebrospinal fluid (CSF) passes and is called the
subarachnoid space.2 Meningitis is an inflammatory disease of
the pia mater and arachnoid membranes including the CSF in
the subarachnoid space and in the cerebral ventricles.2

BACTERIAL MENINGITIS
Bacterial meningitis develops when the virulence of the causative pathogen overcomes the hosts defense mechanisms.
The virulent bacteria are able to colonise the hosts mucosal
epithelium, invade the blood stream, cross the blood brain
barrier and multiply within the CSF.3 The host then initiates an
intense inflammatory response. The inflammatory response
activates other processes which ultimately cause damage to
the subarachnoid space, resulting in neuronal injury. 4
Bacterial meningitis is a medical emergency.5 Despite appropriate
medical therapy, case fatality rates have been reported as follows:
For meningitis caused by Haemophilus influenzae 2% to
5%.6

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For pneumococcal meningitis about 30% but may be as


high as 80% among elderly persons.7
For invasive meningococcal disease 9% to 12%.8
However, neurologic sequelae are common among those who
survive and include seizures, deafness, motor, sensory and
cognitive deficits.3

Presentation
Although the clinical manifestations of bacterial meningitis are
variable and nonspecific, most patients present with fever and
signs of meningeal irritation such as nausea, vomiting, irritability, anorexia, headache, confusion, back pain and the inability
to flex the head forward.5
The clinical presentation of bacterial meningitis depends partly
on the duration of the illness, the hosts response to the infection and the age of the patient.
In adults, a triad of neck stiffness, headache and photophobia occurs in 44% of patients.5
The manifestations seen in older children include fever,
headache, photophobia, nausea, vomiting, confusion, lethargy and irritability.5
In infants, bacterial meningitis may manifest as fever, hypothermia, lethargy, respiratory distress, jaundice, poor feeding, vomiting, diarrhoea, seizures, restlessness, irritability
and /or bulging fontanelle.5

Causative agents
Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae are the most common causes of bacterial
meningitis after the neonatal period. Since the introduction of
H. influenzae type b (Hib) conjugate vaccines, N. meningitidis
and S. pneumoniae have become the most common causes of
bacterial meningitis in the world.1

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MENINGOCOCCAL MENINGITIS9
Thirteen serogroups of N. meningitidis have been identified, five of
which are recognised to cause epidemics, namely serogroups A,
B, C, W-135 and Y. In South Africa, sporadic cases of meningococcal disease are seen throughout the year with a seasonal increase
in winter and early spring. Occasionally, small clusters of cases occur.9 About 400500 cases of meningococcal disease are reported
in South Africa annually. Serogroup W-135 is dominant in Gauteng
while serogroup B is dominant in the Western Cape.9

Meningitis belt

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disease is antibiotic chemoprophylaxis given to close contacts of the infected patient.8 The chemoprophylaxis reduces
nasopharyngeal carriage of N. meningitides.8
Close contacts of a patient with meningococcal meningitis are
defined as:9,12
Those living in the same household
Those who share eating utensils
Those who share a bathroom and or bedroom in a hostel
Those exposed to the respiratory secretions of the patient e.g.
intimate boy or girlfriends, mouth kissing contacts, medical staff

In Africa there is a region which is referred to as the meningitis


Postexposure prophylaxis
belt. This area is in North
recommendations in the
Africa and extends from
If more than one case involving the same serogroup
following:
Senegal to Ethiopia. In
occurs in particular setting such as a school, university,
In the educational setting: 9,12
the meningitis belt, large
hostel, mine etc within a four week period, expert advice
outbreaks and epidemics of
When a single case of meninmust be sought.9
meningitis occur during the
gococcal meningitis occurs,
dry season (i.e. December
it is usually not necessary for
to June). In the meningitis belt serogroup A is most prevalent,
the whole class/school to receive antibiotic chemoprophylaxis.
but serogroups C, X, and W-135 are also found.11
Prophylaxis should be given to close friends who may share
eating utensils or those who fulfill the above criteria of a close
contact. It is difficult to determine who the close contacts are
Transmission
of a young child in a crche or preschool. Where possible,
N. meningitides colonises the mucosa of the nasopharynx. It
chemoprophylaxis should be given to those children who meet
is transmitted through direct contact with respiratory secrethe above-mentioned criteria.
tions of an infected patient or from an asymptomatic carrier.9
Healthcare workers: 9,12 Healthcare workers who are lookAbout 10% of the population are thought to be asymptomatic
carriers.12 Asymptomatic carriers develop systemic immunity to
ing after a case of meningococcal meningitis do not need
prophylaxis unless they have been directly exposed to the
meningococcus about 14 days after acquiring the bacteria. Innasopharyngeal secretions of the patient. Exposure may
vasive disease only occurs in the minority of people.9 Asymptooccur through mouth-to-mouth resuscitation or during enmatic carriers rather than patients with meningococcal disease
dotracheal intubation. Healthcare workers can reduce their
are usually the source of new infections.9
risk of exposure to the droplet secretions by using appropriate barrier nursing techniques.
Risk factors8,9
In the work setting:9,12 Working with a patient with meningococIndividuals at an increased risk of acquiring meningococcal
meningitis include:
cal meningitis is not necessarily considered a close contact
Children under 5 years of age
unless they meet the above mentioned close contact criteria.
Young adults
Household contacts of a patient with meningococcal
Meningococcal meningitis chemoprophylaxis
meningitis
The chance of a second case of meningococcal meningitis oc Coexisting viral infection
curring in a close contact of an index case is greatest immedi Overcrowded living conditions
ately after the onset of disease in the index case. Therefore,
Active or passive smoking
recommended antibiotic prophylaxis should be given within 24
Students attending university or technikon for the first time
hours of the index case being identified. Prophylaxis may be
and living in residences or hostels
effective up to 1014 days after exposure.8,9
Military recruits or police living together in barracks or
hostels
In South Africa ciprofloxacin is the drug of choice for post expo Patients with immune system deficiencies such as those
sure prophylaxis of meningococcal meningitis.9,12
with terminal common complement pathway deficiencies,
For adults a stat dose of 500 mg is indicated.
functional or anatomic asplenia.
For children a stat dose of 10 mg/kg (up to a maximum
Coexisting Human Immunodeficiency Virus (HIV) infection
dose of 500 mg) is indicated. Note: Ciprofloxacin is usuNonetheless, most cases of meningococcal meningitis do not
ally contra-indicated in children but meningitis treatment
have an identifiable cause.9
guidelines recommend its use as meningococcal meningitis
chemoprophylaxis in children.
Ceftriaxone is an alternative antibiotic for use in pregnant
Meningococcal meningitis prevention
women. The dose is 250 mg given by intramuscular injection.13
The primary means for prevention of sporadic meningococcal

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Vaccination8,9
There are two vaccines available in South Africa against
meningococcal meningitis namely Menomune and
Mencevax. Both vaccines are polysaccharide vaccines and
are protective against the serogroups A, C, W-135 and Y.
There is no vaccine available against the B serogroup.
Polysaccharide vaccines are of limited benefit in children under
two years of age.
Vaccines are given to prevent future infection. They are not
indicated for post-exposure prophylaxis after a single case of
meningococcal meningitis. However, they are indicated in a
confirmed outbreak situation.9
Vaccination against meningococcal meningitis is not routinely
performed in South Africa. However, it is recommended in
certain circumstances such as8,9:
Long term travellers to the meningitis belt
Pilgrims going to Hajj or Umrah
Individuals with functional or actual asplenia
Individuals with terminal common complement pathway
deficiencies
Laboratory staff working with N. meningitidis
A confirmed outbreak setting

MENINGITIS CAUSED BY STREPTOCOCCUS


PNEUMONIAE
Transmission of S. pneumoniae is through direct personto-person contact with infected respiratory droplets and by
autoinoculation in a person carrying the bacteria in their upper
respiratory tract.7 Pneumococci are commonly found in the
respiratory tract. Rates of asymptomatic carriage vary with age,
the environment and the presence of an upper respiratory tract
infection.7 Pneumococci may be isolated from the nasopharynx
of 5%70% of healthy adults.7 In many parts of the world, at
any given time over 50% of children under three years of age
are colonised with pneumococcus.14 S. pneumoniae is now
the leading cause of bacterial meningitis in children under five
years of age.7

Prevention
Pneumococcal meningitis can be prevented by vaccination.

Routine vaccination
Children under two years of age, and adults over 65 years of age
are at increased risk of invasive pneumococcal disease and it is
recommended that these age groups be routinely vaccinated.17
In South Africa there are four pneumococcal vaccines available:15
a. A conjugated-7-valent pneumococcal vaccine (PCV7) called
Prevenar for use in all infants and young children. Prevenar
was introduced into the South African market in 200515 and was
incorporated into the EPI in 2009.16 Prevenar is registered to
be given at 6, 10 and 14 weeks of age and a booster dose in
the second year of life.18 In the EPI however, it is given at 6 and

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14 weeks with a booster dose given at nine months of age.16


Prevenar is registered for use up to the age of nine years.18
b. There are two polysaccharide pneumococcal vaccines
(PPV23) namely Imovax-pneumo 23 and Pneumovax for
use in high risk patients over two years of age. Individuals
over the age of 65 years receive one dose of the polysaccharide pneumococcal vaccine.17
c. A 10-valent pneumococcal vaccine, using a recombinant
form of protein D has recently been registered called Synflorix. The immunisation schedule for babies aged six weeks
to six months consists of three doses given one month apart
with a booster dose at least six months after the last primary
dose, preferably between 1215 months of age.30

Vaccination of high-risk groups


Besides the above-mentioned age groups there are certain
individuals who are at an increased risk of invasive pneumococcal disease. This includes7,19:
Individuals with
Chronic cardiovascular disease (e.g. heart failure,
cardiomyopathy).
Chronic pulmonary disease (e.g. chronic obstructive
pulmonary disease, emphysema and asthma).
Chronic liver disease (e.g. cirrhosis).
Chronic renal failure or nephrotic syndrome.
Diabetes mellitus.
Functional or anatomic asplenia (e.g. sickle cell disease, splenectomy).
Immunosuppressive conditions (e.g. HIV infection, congenital immunodeficiency, malignancy, B-cell defects,
multiple myeloma).
Solid organ or haematopoietic cell transplant recipients.
Patients undergoing treatment with alkylating agents, antimetabolites, or systemic corticosteroids.
Patients with cerebrospinal fluid leaks.
Cochlear implant recipients.
Patients who smoke.
Individuals living in an institution.
Adults with any of the risk factors should receive 1 dose of PPV23.19
In addition to a full course of Prevenar, children over 24 months
of age with any of these risk factors should also receive 1 dose of
PPV23 at least two months after their last Prevenar dose.20
It is not necessary to revaccinate immunocompetent individuals who fall within the high risk groups.19 One dose of PPV23 is
sufficient. However, individuals at highest risk of invasive pneumococcal disease should receive a second PPV23 vaccine 5
years after the first dose of PPV23. This includes patients19:
Who are immunocompromised
With functional or anatomic asplenia
With Sickle cell disease
Antibiotic chemoprohylaxis does not play a role in prevention of
the spread of pneumococcal disease.21

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MENINGITIS CAUSED BY HAEMOPHILUS


INFLUENZAE

lead to secondary transmission of disease.6

H. influenzae type b (Hib) was the leading cause of bacterial meningitis among children younger than five years of age
before an effective vaccine against Hib was developed.6 It was
responsible for 5065% of all cases of meningitis in the prevaccination era.6 Nearly all Hib infections occurred among children
younger than five years of age, and approximately two-thirds
of all cases occurred among children younger than 18 months
of age.6 Diseases caused by Hib are not commonly seen in
patients over five years of age.6 Hib is transmitted from personto-person via infected respiratory secretions.4,6

Close contacts of a patient with invasive Hib disease who receives antibiotic chemoprophylaxis soon after the index patient
is diagnosed, will remove pharyngeal carriage of Hib. This will
a. reduce the risk of developing invasive disease if they are
not immune and
b. prevent further spread of the disease.27

Prevention

A close contact in this instance is defined as a person living


in the same house as the index case or spending more than
four hours a day with the index case for five out of seven days
before the index case was admitted to hospital.27

A vaccine against Hib was introduced into the routine childhood


immunisation programmes in many countries resulting in diseases
caused by Hib being practically eliminated in these countries.22
The Hib vaccine was introduced into the South African Expanded
Program of Immunisation (EPI) in 1999.23 In the first five years
following the introduction of the Hib vaccine into the EPI, cases of
invasive Hib disease were significantly reduced.24 A booster dose
at 18 months was introduced into the EPI in 2009.16

Chemoprophylaxis is recommended in the following situations4,27:


For all household/close contacts when there is at least one
contact under four years of age who has not been fully
vaccinated.
For all household/close contacts with a contact who is an
immunocompromised child.
For childcare centre contacts when two or more cases of
invasive Hib disease have occurred within 60 days.

Vaccination

Pharyngeal carriage in the index case should be eliminated if


the child is under two years of age, or if he lives with a child
under four years of age who has not been fully vaccinated.27

There is a vaccine available called Hiberix which only protects


against disease caused by Hib. However, Hib is usually given
in a combination vaccine along with diphtheria, tetanus, pertussis and polio from 6, 10 and 14 weeks of age or at 8, 12 and 16
weeks of age.25,26 A booster dose is indicated at 18 months of
age.16 This again is given in combination.
The clinical efficacy after a primary series of Hib vaccines is
estimated to be between 95100%. It is uncommon for a fully
vaccinated baby to develop invasive Hib disease.6 Children
who develop invasive Hib disease after receiving a full course
of Hib vaccines should undergo immunologic evaluation.27
In general, it is not necessary to vaccinate individuals over five
years of age against Hib, as most individuals would already be
immune due to a previous asymptomatic infection.6
However, there are certain people who are at a higher risk of
contracting invasive Hib disease. These include6:
Individuals with functional or anatomic asplenia
Individuals with immunodeficiency
Immunosuppression due to cancer chemotherapy or HIV
infection
Recipients of a haematopoietic stem cell transplant.
It is recommended that patients over five years of age who did
not receive Hib in infancy and who fall into the above high risk
groups receive one dose of Hib vaccine.6

Post exposure prophylaxis


Although the incidence of meningitis caused by Hib has been
reduced by vaccination, it still occurs. Invasive Hib disease is
not highly contagious but close contact with an index case can

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Children under two years of age do not develop an adequate immune response to Hib invasive disease and therefore still need
to either start vaccination or continue vaccination against Hib
once they have been discharged from hospital.28 It is expected
that children over two years of age will develop protective immunity after infection and do not need vaccination against Hib.27

Drug of choice27,29
Rifampicin is recommended to eliminate pharyngeal carriage
of Hib. Over one month of age the dose is 20 mg/kg (up to a
maximum dose of 600 mg) per day for four days. Under one
month of age a dose of 10 mg/kg per day for four days is used.

In conclusion
Bacterial meningitis is a potentially life threatening disease. In
patients who survive, there is a risk of permanent sequelae.
Meningitis caused by Haemophilus influenzae has been dramatically reduced in countries where routine vaccination has been
implemented including South Africa. Invasive pneumococcal
disease can be prevented by routine vaccination of PCV7 for
young children and by vaccinating high-risk individuals with
PPV23. The spread of sporadic cases of meningococcal meningitis is prevented by administration of chemoprophylaxis to close
contacts of the patient. Vaccination and chemoprophylaxis play
a key role in the prevention of the three most common causes of
bacterial meningitis namely Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae.r

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