MENINGITIS C VACCINE

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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 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 2-8^oC 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:

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.

23.4.1 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:

(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

· Fever (2-4%)

· Fever (5%)

(4-11 yr.)

· Headaches (10%)

· Headaches (14%)

23.5.2. The rates of local reactions such as redness and swelling increase with age.

23.5.3 The rates of systemic reactions with MenC conjugate (shown above) were no higher than the background rates of other routinely administered vaccines at those ages, suggesting that MenC conjugate adds very little in the way of systemic reactions. Systemic reactions such as fever are less common than local reactions in all age groups.

23.5.4 All suspected adverse reactions after the administration of the MenC conjugate vaccine should be reported to the Committee on Safety of Medicines using the yellow card system.

Meningococcal Plain Polysaccharide A&C Vaccine

23.5.5 Generalised reactions are rare although pyrexia occurs more frequently in young children than in adults.

23.5.6 Injection site reactions occur in approximately 10% of recipients and last for approximately 24-48 hours.

23.5.7 Serious suspected reactions, including those which are fatal, life threatening, disabling, incapacitating or which result in hospitalisation should be reported. (See 8.1.4)

23.6 Contraindications

23.6.1 Immunisation should be postponed in individuals suffering from an acute febrile illness.

23.6.2 Although there is no information to suggest that meningococcal vaccination (MenC conjugate or meningococcal plain polysaccharide A&C vaccine) is unsafe during pregnancy, it should not be given unless there is high risk of the individual developing the disease.

23.6.3 A hypersensitivity reaction to any constituent of the vaccine including meningococcal C polysaccharide, diphtheria toxoid or the CRM197 carrier protein, or tetanus toxoid is a contraindication.

The following meningococcal vaccines are licensed and available:-

Meningococcal plain polysaccharide A&C vaccines

Mengivac (A&C), Pasteur Merieux MSD Ltd

Telephone 01628 773200

AC Vax, SmithKline Beecham

Telephone 0800 616482

Meningococcal conjugate Group C vaccine

Meningitec, Wyeth Laboratories

Telephone 01628 604377

This is supplied by Farillon (Telephone 01708 379000) as part of the National Childhood Immunisation Programme.

[Subject to licensure and availability, meningitis C conjugate vaccines may be available from Chiron Vaccines and North American Vaccines]

23.8 Bibliography

Antibody response to serogroup A&C polysaccharide vaccines in infants born to mothers vaccinated during pregnancy.
McCormick J B, Gusman H H et al.
J of Clin. Investigation, 1980; 65 : 1141-1144.

Meningococcus Group A vaccine in children three months to five years of age. Adverse reactions and immunogenicity related to endotoxin content and molecular weight of the polysaccharide.
Peltola H, Kayhty H, Kuronen T, Haque N, Sanna S, Makela P H.
J. Pediatr. 1978; 92 : 818-822.

Kinetics of antibody production to Group A and Group C meningococcal polysaccharide vaccines administered during the first six years of life; prospects for routine immunisation of infants and children.
Gold R, Lepow M L, Goldschneider I, Draper T F, Gotschlich E C.
J Infect Dis 1979; 140 : 690-7.

Secondary cases of meningococcal infection among close family and household contacts in England and Wales, 1984-7.
Cooke R P D, Riordan T, Jones D M, Painter M J.
BMJ 1989; 298: 555-558.

Control of meningococcal disease: guidance for Consultants in Communicable Disease Control, PHLS Meningococcal Infections Working Group and Public Health Medicine Environmental Group. CDR Review 1995:5(R13):R189-195
Control of meningococcal disease : guidance for microbiologists
Kaczmarski E B, Cartwright KAV, CDR Review 1995;5(R13):R196-98

Lepow ML., Perkins BA., Hughes PA., Poolman JT. Chapter 28: Meningococcal Vaccines. In; Vaccines, 3rd Edition, Plotkin & Orenstein, Saunders, 1999: 711-727.
Cartwright K, ed. Meningococcal disease. Chichester, UK: John Wiley & Sons, 1995
Ramsay M., Kaczmarski E., Rush M., Mallard R., Farrington P., White J. Changing patterns of case ascertainment and trends in meningococcal disease in England and Wales. CDR Rev. 1997; 7:R49-54.
MacDonald EM., Haplerin SA., Law JL., Forrest., Danzig LE., Granoff DM. Induction of Immunologic Memory by Conjugated vs Plain Meningococcal C Polysaccharide Vaccine in Toddlers. A Randomised Controlled Trial. JAMA. 1998; 280:1685-1689.

Richmond P., Borrow R., Miller E., Clark S., Sadler F., Fox A., Begg N., Morris R., Cartwright K. Meningococcal Serogroup C Conjugate Vaccine is Immunogenic in Infancy and Primes for Memory. J. Infect. Dis. 1999;179:1569-72.