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Meningococcal vaccines |
Summary
In Australia, most cases of invasive meningococcal disease are caused by Neisseria meningitidis serogroup B for which there is currently no vaccine. Serogroup C infection comprises about one third of cases, but its incidence varies between the states and between age groups. Serogroup A rarely occurs in Australia. Polysaccharide vaccines which give short-term protection against serogroups A, C, W135 and Y have been available for many years. These vaccines are mainly used for travellers to regions where serogroup A and W135 infections are prevalent, but they can also be used in outbreak control. The new conjugated serotype C vaccines are highly effective, have a low rate of adverse events and induce immunologic memory. They will be used in mass vaccination programs in Australia from 2003, but they only protect against serotype C infection.
Key words: meningitis, immunisation.
(Aust Prescr 2003;26:56-8)
Introduction
Each year in Australia, meningococcal infections cause 700-800 hospitalisationsand 35-40 deaths (10 in children aged 0-4 years). Invasive diseaseusually presents as meningitis or septicaemia. The mortality is high and thosewho survive may have severe sequelae.1,2
Epidemiology
The causative organism (Neisseria meningitidis)is carried asymptomatically by about 20% of the population.1,2 Itis spread by the respiratory route. In Australia in 2001 the incidence of meningococcaldisease was about 3.5 cases per 100 000 population, but the rate in indigenouspeople is nearly six times higher. People with inherited defects of properdinor complement, or functional or anatomic asplenia, are at increased risk ofmeningococcal infection. The highest attack rate is in children aged 0-4years and young adults 15-24 years. In Australia, there is a distinctseasonality with peak incidence in winter and spring.1,2 Thecourse of the illness is often rapid and dramatic.
Microbiology
Neisseria meningitidis has 13 serogroups.2 Withina serogroup there are often many serotypes and subtypes identifiable by differencesin outer membrane proteins. The serogroups currently responsible for most invasivedisease internationally are A, B, C, W135 and Y.
In Australia serogroup B causes most infections and serogroup C about onethird of cases (Fig. 1). However, an increase in the rateof serogroup C infections has been noted over the past seven years. There aremarked differences in serogroup C rates from state to state, with New SouthWales and Victoria experiencing the largest recent increases.3 Thenumber of notifications of serogroup C disease exceeded the number of notificationsof serogroup B disease in Victoria in 2000 and 2001 (Fig. 2).4 Increasingrates of serogroup C infection have also been seen in the UK and North America.
Serogroup A disease has rarely been seen in Australia since a small outbreakin the early 1990s, but occurs regularly in Africa and Asia. Serogroup W135has recently been seen in Africa and in pilgrims to the Hajj. New Zealand hasbeen experiencing an outbreak of serogroup B disease since 1991 with ratesof type B disease nearly 10 times higher than those reported in Australia.5
Vaccines
There are two quite different types of meningococcal vaccines. The multivalentpolysaccharide vaccine (containing polysaccharides from serogroups A, C, W135,Y) has been available for many years. It is frequently used in adults and olderchildren travelling to endemic areas of Africa and Asia. The new conjugatedserogroup C vaccine is effective in young children.
There is no vaccine forserogroup B. A prototype vaccine especially developed for the subtype (B:4:P1.7b,4)prevalent in New Zealand is currently being studiedin Auckland.5
Meningococcal tetravalent polysaccharide vaccine
There are two products available (Mencevax ACWY - containing phenol 0.25%as a preservative, and Menomune - containing thiomersal 0.01% as a preservative).Each protects against serogroups A, C, W135 and Y. These vaccines are providedin a monodose vial with 0.5 mL saline diluent.2 Theydo not contain infectious material.
These tetravalent polysaccharide vaccines can be used for travellers and inoutbreak control although the conjugated vaccine would be preferred for controlof serogroup C outbreaks. Polysaccharide vaccines are not suitable for massvaccination programs because:
– children under the age of 10 years have a diminished immunologic responseand the vaccines are not approved for use in children under the age of twoyears
– immunity persists for only 3-5 years depending on the age ofthe recipient
– hyporesponsiveness occurs following subsequent doses
– effectiveness against serogroup C disease varies according to ageand length of follow-up (one study showed 65% effectiveness for two years inpeople aged six months-20 years).
Adverse events such as injection site reactions and fever, which occur in2% of children, are usually mild. Contraindications are hypersensitivity toany of the vaccine components or anaphylactic reaction following a previousdose.2
Meningococcal serogroup C conjugate vaccine
There are three products available:
– Meningitec - the 0.5 mL dose contains group C oligosaccharideconjugated to 15 microgram of non-toxic Corynebacteriumdiphtheriae CRM197 protein + aluminiumphosphate adjuvant
– Menjugate - the 0.5 mL dose contains group C polysaccharide conjugatedto 12.5-25 microgram of a non-toxic Corynebacteriumdiphtheriae CRM197 protein + aluminiumhydroxide adjuvant
– NeisVac-C - the 0.5 mL dose contains group C polysaccharide conjugatedto 10-20 microgram of tetanus toxoid + aluminium hydroxide adjuvant.
These vaccines contain no infectious material and have some important features:
– they can be given to all age groups including infants from the ageof six weeks
– only a single dose is required for people over one year old (babiesunder the age of four months require three doses at least one month apart;those aged over four months but less than 12 months old require two doses*)
– the effectiveness is about 90% in the short term6,7
– they may have a long duration of protection - possibly 15 ormore years.
Adverse event rates vary with the age of the child. Children under the ageof two years can develop local redness (2%), irritability (20-50%) andfever more than 380C (2-5%). Older children more frequently developlocal redness (30%) and headaches (10-14%), but have a slightly lowerrate of fever (1-2%).3,6
The vaccines are contraindicated in people with a hypersensitivity to anyof the components or an anaphylactic reaction to a previous dose. They arenot recommended in pregnancy (Category 2B) due to lack of data.
The vaccines may be administered simultaneously with other vaccines in theAustralian Standard Vaccination Schedule. They should not be mixed in the samesyringe with other vaccines.
Meningococcal serogroup C vaccination programs
A mass vaccination program using conjugated meningococcal C vaccines beganin the UK in November 1999.6 Theprogram offered vaccine progressively to everyone aged less than 18 years andthere has been a very high uptake (80%). The UK program has resulted in a reductionof at least 75% in serotype C disease in the vaccinated age groups. While thereis evidence of herd immunity in these age groups, there has been no evidenceof herd immunity in other age groups.6,7
The Australian Government has announced approval for a meningococcal C vaccinationprogram to commence in 2003. The conjugated vaccine has been included in theAustralian Standard Vaccination Schedule for all children reaching the ageof one year. In 2003 the vaccine will also be offered in a catch-up programto children aged one to five years by general practitioners and to senior highschool children in a school-based program. In 2004-05 the remaining school-agechildren will have the opportunity to receive the vaccine in school-based programs.The rapidity of implementation of school-based programs will vary between jurisdictions.In view of the excellent response to the Measles Control Campaign, these school-basedprograms are likely to be popular.
The community must understand that this program will only prevent serogroupC disease. It will take several years to make a significant impact on groupC disease and the 200 cases and 18 deaths which group C infection causes nationallyeach year (Fig. 1).
E-mail: margarb1@chw.edu.au
* The National Health and Medical Research Council (NHMRC)recommends two doses, but this conflicts with the product information whichrecommends three doses in this age group. The NHMRC recommendations shouldbe followed.
References
1. McIntyre P, Gidding H, Gilmour R, Lawrence G, HullB, Horby P, et al. Vaccine preventable diseases and vaccination coverage inAustralia, 1999 to 2000. Commun Dis Intell 2002;Suppl:1-111.
http://www.health.gov.au/pubhlth/cdi/pubs/pdf/vpd99_00.pdf
2. Australian Technical Advisory Group on Immunisation.The Australian Immunisation Handbook. 7th ed. Canberra: National Health andMedical Research Council; 2000.
http://immunise.health.gov.au/handbook_7.pdf
3. Australian Technical Advisory Group on Immunisation.Recommendations on the use of meningococcal C conjugate vaccine in the Australianpopulation. Canberra: Department of Health and Ageing. In press 2003.
4. Lester R, Pitcher H, Pellissier S, Robinson P. Vaccinationagainst serogroup C meningococcal disease. Vic Infect Dis Bull 2002;5:26-8.
5. Baker MG, Martin DR, Kieft CE, Lennon D. A 10-yearserogroup B meningococcal disease epidemic in New Zealand: descriptive epidemiology,1991-2000. J Paediatr Child Health 2001;37:S13-S19.
6. Miller E, Salisbury D, Ramsay M. Planning, registration,and implementation of an immunisation campaign against meningococcal serogroupC disease in the UK: a success story. Vaccine 2001;20 Suppl 1:S58-67.
7. Ramsay ME, Andrews N, Kaczmarski EB, Miller E. Efficacyof meningococcal serogroup C conjugate vaccine in teenagers and toddlers inEngland. Lancet 2001;357:195-6.
Conflict of interest: none declared
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