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Chapter for "Immunisation Against Infectious Disease 1996" - Chapter 23
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REPLACEMENT CHAPTER FOR "IMMUNISATION AGAINST INFECTIOUS
DISEASE" 1996
CHAPTER 23
MENINGOCOCCAL
23.1 Introduction
23.1.1 Meningococcal meningitis and septicaemia are
systemic infections caused by Neisseria meningitidis. Meningococci
are Gram negative diplococci, which are divided into antigenically distinct
groups. There are at least 13 serogroups known, of which Groups B and C are
the commonest in the UK. Other less common serogroups include A, Y, W-135,
29E and Z. These 13 serogroups are further subdivided by serotype and
sulphonamide sensitivity.
23.1.2 In the past, Group B strains accounted for
approximately two thirds of all isolates submitted to the Public Health
Laboratory Service Meningococcal Reference Laboratory. Group C strains
usually contribute about one third, but over the past few years the
proportion has risen to 40%. Group A strains are rare in this country (less
than 2%) but are the epidemic strains in other parts of the world.
23.1.3 Irregular upsurges of meningococcal disease
have occurred throughout the last 80 years. Over the past five years, the
pattern of meningococcal disease has changed with an overall increase in the
number of laboratory confirmed cases. In 1998/99 the number of notifications
was 2962 compared to 1555 in 1994/95. These figures relate to
epidemiological years, which run from 1st July to 30th June. Although some
of this increase may be due to improvements in reporting, it is likely that
this represents a real increase. The most recent increase in meningococcal
disease has been associated with an increased incidence of Group C disease
in teenagers and young adults among whom case fatality rates are
particularly high. This increase has been due to an increased prevalence of
the C2a serotype.
23.1.4 The incidence of meningococcal disease is
highest in infants under 1 year of age followed closely by children aged 1-5
years. The next highest risk group is young people aged 15-19 years. Whilst
the incidence is greatest in the under 1s, mortality for Group C disease is
highest in the teenage years.
23.1.5. There is a marked seasonal variation in
meningococcal disease with peak levels in the winter months declining to low
levels by late summer. An association has been demonstrated between the
seasonal onset of influenza activity and meningococcal disease in some
seasons.
23.1.6 The carriage rate for all meningococci
varies with age. In infants and young children the carriage rate is low. In
adults, the carriage is usually about 5-11%, but up to 25% of young adults
may be carriers at any one time.
23.1.7 Meningococci are transmitted by
droplet spread or direct contact from carriers or from individuals in the
early stages of the illness; the probable route of invasion is via the
nasopharynx. The incubation period is from two to as long as seven days, and
the onset of disease varies from fulminant to insidious with mild prodromal
symptoms. Early symptoms and signs are usually malaise, pyrexia and
vomiting. Headache, photophobia, drowsiness or confusion, joint pains and a
typical haemorrhagic rash of meningococcal septicaemia may develop. Early
on, the rash may be non-specific. Later in the illness, the rash, which
may be petechial or purpuric, does not blanche and this can readily be
confirmed by gentle pressure with a glass, when the rash can be seen to
persist. Patients may present in coma. In young infants particularly, the
onset may be insidious and the classical signs absent. The diagnosis should
be suspected in the presence of vomiting, pyrexia, irritability and, if
still patent, raised anterior fontanelle tension.
23.1.8 Overall mortality from meningococcal
infection is around 10% and has changed little for the last 20 years.
Meningitis is the commonest presentation, but in about 15-20% of cases,
features of septicaemia predominate. Mortality is 7% in meningitis and 20%
in septicaemia. Current expert advice endorses the importance of early
recognition, prompt antibiotic treatment and speedy referral to hospital for
all suspected cases. Benzylpenicillin is the antibiotic of choice and should
be administered by the general practitioner before transfer to hospital. The
recommended dose is 1,200 mg for adults and children aged 10 years or more,
600 mg for children aged 1 to 9 years, and 300 mg for those aged less than 1
year. Benzylpenicillin should be withheld if there is a known history of
anaphylaxis following previous penicillin administration. Although
benzylpenicillin may reduce the chance of isolating the causative organism,
this is outweighed by the benefit to the patient, and new techniques are
becoming available that facilitate the diagnosis of meningococcal disease
even after antibiotics have been given.
Graph 1: Number of notifications of meningococcal disease to ONS in
England and Wales (1912-1998
GRAPH 2
GRAPH 3
23.2 Vaccine
23.2.1 Before the introduction of the new
meningococcal C conjugate vaccine (MenC), the plain polysaccharide
meningococcal vaccine was the only vaccine available against Group C
disease. At present there is no available vaccine effective against Group
B organisms.
23.2.2 The meningococcal plain polysaccharide A&C
vaccine is a purified, heat stable, lyophilised extract from the
polysaccharide outer capsule of Neisseria meningitidis, effective
against serogroup group A and C organisms. Vaccine contains 50mcg each of
the respective purified bacterial capsular polysaccharides.
23.2.3 A serological response is detected in more
than 90% of recipients and occurs five to seven days after a single
injection. The response is strictly Group specific and confers no protection
against Group B organisms. Young infants respond less well than adults do
with little response to the Group C polysaccharide below 18 months and
similar lack of response to group A polysaccharide below three months.
Vaccine induced immunity lasts approximately three to five years; in younger
children a more rapid decline in antibody has been noted.
23.2.4The new MenC conjugate vaccine uses the same
technology that was applied to the development of the Hib conjugate vaccine.
Whilst the vaccine is new, the constituents of the vaccines are not and have
been used for a number of years. The technique called conjugation involves
attaching a carrier protein to the polysaccharide antigen formed from the
sugar coat of the bacteria. The carrier proteins used in the new MenC
conjugate vaccines are the variant diphtheria toxin (CRM197) or tetanus
toxoid. The resultant vaccine induces a T-cell dependent antibody response
and immunological memory and is protective in children under 2 years of age.
This vaccine therefore, overcomes the limitations of the meningococcal plain
polysaccharide A&C vaccine. The UK will be the first country to introduce
MenC conjugate vaccine.
23.2.5 Vaccine must be stored at 2-8oC
and must not be frozen. The new meningococcal C conjugate vaccine is
available as a suspension. The meningococcal plain polysaccharide A&C
vaccine should be reconstituted immediately before use with the diluent
supplied by the manufacturer. After reconstitution the vaccine must be used
within one hour. Discard any vaccine which is unused one hour following
reconstitution. NB: The diluent must not be frozen.
23.3 Route of administration and dosage:
23.3.1 Meningococcal plain polysaccharide A&C vaccine
A single dose of 0.5ml is given by deep subcutaneous
injection to adults and children over 2 months of age, but note that the
vaccine should not be given to children aged under 18 months except for
protection against Group A meningitis. Clinical data has confirmed the
efficacy of the serogroup A component over 3 months of age. The response to
the serogroup C component is only transitory.
23.3.2 Meningococcal conjugate Group C vaccine
A single dose of 0.5ml is given by intramuscular or deep
subcutaneous injection to individuals aged 1 year and over. For infants,
doses are given at 2, 3 and 4 months of age. Based on the results of PHLS
studies on immunogenicity, and experiences from the use of Hib vaccine,
those over 4 months and under 12 months should have two doses. The vaccine
is given preferably in the anterolateral thigh in infants and in the deltoid
region in older children, adolescents and adults.
In patients with thrombocytopenia or bleeding disorders
the vaccine may be given subcutaneously.
23.4 Recommendations
23.4.1 Immunisation with MenC conjugate vaccine will
become part of the routine Childhood Immunisation Programme in the UK from
autumn 1999. MenC conjugate vaccine will be given at the same time as
primary immunisation with DTP/Hib, and polio immunisation. Each infant will
receive a dose at 2, 3 and 4 months of age. The highest risk groups will be
targeted first to receive MenC conjugate vaccine followed by those at lower
risk.
23.4.2 Data from PHLS studies show that excellent
antibody responses are generated when MenC conjugate vaccine is given 6
months after meningococcal plain polysaccharide A&C vaccine. No data are
available to confirm the same effects within 6 months.
23.4.3 Meningitis C conjugate vaccine should not
be used for travel purposes as the greatest risk is from group A infection.
23.4.4 Contacts of cases: Close contacts of
cases of meningococcal infection have a considerably increased risk of
developing the disease in the subsequent months, despite appropriate
chemoprophylaxis. The recommended schedule for prophylaxis is rifampicin
600mg every 12 hours for two days in adults, 10mg/kg dose for children over
one year of age and 5mg/kg for children less than one year. Ciprofloxacin as
a single dose of 500mg is an alternative for adults but is not yet licensed
in the UK for this purpose. Ceftriaxone 250mg intramuscularly can be given
to pregnant contacts, but is not licensed in the UK for this purpose.
Immediate family or close contacts of cases of Group A or Group C meningitis
should be given meningococcal vaccine in addition to chemoprophylaxis. Until
there are sufficient stocks of meningitis C conjugate vaccine, meningococcal
plain polysaccharide A&C vaccine should be used, except in contacts (as
above) who are under 2 years of age. This policy will be reviewed as reserve
stocks accummulate. Chemoprophylaxis should be given first and the decision
to offer vaccine should be made when the results of typing are available.
Vaccine should not be given to contacts of Group B cases.
23.4.5 Local Outbreaks: In addition to
sporadic cases, outbreaks of meningococcal infections with Group C organisms
tend to occur in closed or semi-closed communities such as schools and
military establishments. Immunisation with meningococcal plain
polysaccharide A&C vaccine has been shown to be effective in controlling
epidemics, reducing disease rates, but not carriage rates. This vaccine
should be used until stocks of meningitis C conjugate accummulate (see
above). Advice on the use of meningococcal vaccines is available from:-
PHLS Communicable Disease Surveillance Centre
(Telephone: 0181-200 6868), or CDSC Regional Units
Public Health Laboratory Service
Meningococcal Reference Laboratory
(Telephone: 0161 445 2416).
Scottish Centre for Infection and Environmental Health
(Telephone: 0141 946 7120).
Scottish Meningococcal and Pneumococcal Reference
(Scotland) Laboratory
(Telephone: 0141 201 3836).
Meningococcal vaccine has no part to play in the
management of outbreaks of Group B meningococcal meningitis.
23.4.6 Travel: In some areas of the world
the risk of acquiring meningococcal infection is much higher, particularly
of developing Group A disease, than in this country particularly for those
visitors who live or travel 'rough', such as backpackers, and those living
or working with local people. Immunisation is recommended for longer visits
(generally a month or more), especially if backpacking or living or working
with local people, to:
(i) Sub-Saharan Africa:
Epidemics, mainly Group A infections, occur throughout
tropical Africa particularly in the Savanna in the dry season which varies
from country to country and can be unpredictable. More detailed country by
country information is contained in the UK Health Departments' book
`Health Information for Overseas Travel'.
(ii) the area around Delhi, and Nepal, Bhuntan and
Pakistan.
(iii) Since 1988, following an outbreak of Group A
meningococcal meningitis in 1987, Saudi Arabia has required immunisation of
people coming to the Haj annual pilgrimage.
NB: The new MenC conjugate vaccine protects against
Group C disease only. Individuals travelling abroad (listed above) should be
immunised with the Meningococcal plain polysaccharide A&C vaccine, even if
they have received the MenC conjugate vaccine before.
23.4.7 Meningococcal vaccine may be given to HIV
positive individuals in the absence of contraindications.
23.5 Adverse Reactions
MenC Conjugate Vaccine
23.5.1 The rates of local reactions and systemic
reactions after MenC conjugate vaccine are similar to those seen with Hib
vaccine. The most common reactions seen are redness and swelling at site of
injection, mild fevers, irritability, and headaches. The frequency of these
reactions (expressed as a percentage) for each age group are shown in the
following table.
MenC Conjugate Vaccine |
