Vaccines
A Short Review of Serogroup C Meningococcal Conjugate Vaccines Helen Campbell1
and Mary Ramsay2 1. Senior Clinical Scientist; 2. Head, Immunisation Department, Health Protection Agency Centre for Infections
Abstract
From the mid-1980s, a disproportionate increase in serogroup C meningococcal disease associated with a highly virulent strain was observed in a number of countries. As licensed polysaccharide vaccines available at that time could not protect young children and did not provide long-term protection at any age, there was an accelerated development of meningococcal C conjugate (MenC) vaccines. MenC vaccines were introduced into national childhood programmes from late 1999 onwards, usually together with mass catch-up campaigns. MenC vaccine programmes have successfully controlled serogroup C disease in those directly protected through immunisation and, importantly, have also reduced carriage, thereby inducing a herd immunity effect and protecting the wider population. The safety of MenC vaccines was demonstrated in clinical trials and post-licensure evaluation. High levels of effectiveness a year after infant primary immunisation are not sustained, which has led to schedule changes, but protection is better maintained in older age groups and disease control remains good, largely due to the impact on carriage.
Keywords Meningococcal serogroup C disease, meningococcal C conjugate vaccine, surveillance, immunisation, epidemiology
Disclosure: The Immunisation, Hepatitis and Blood Safety Department of the Health Protection Agency occasionally receives research grants and cost-recovery payment for provision of post-marketing surveillance reports from vaccine manufacturers. HC has provided consultancy advice to vaccine manufacturers without personal payment. Acknowledgments: The authors would like to thank all those who contributed to EU-IBIS and to the management and compilation of these data (
www.hpa-bioinformatics.org.uk/euibis). Received: 20 January 2011 Accepted: 18 March 2011 Citation: European Infectious Disease, 2011;5(2):129–34 Correspondence: Helen Campbell, Immunisation, Hepatitis and Blood Safety Department, Health Protection Agency Centre for Infections, 61 Colindale Avenue, London, NW9 5EQ, UK. E:
helen.campbell@
hpa.org.uk
Meningococcal Disease
Invasive meningococcal disease most commonly presents as meningitis or septicaemia. However, invasive disease is a rare outcome of infection and most people who are infected become asymptomatic carriers. The carrier state may last from a few days to several months; it provides a reservoir for infection and enhances the immunity of the host. When invasive disease does arise, onset is usually sudden and can progress rapidly. The case fatality rate is high, but varies according to a number of factors including the serogroup, the patient’s age and the disease presentation. Long-term complications, including brain damage, deafness, seizures and amputation, are also common in survivors.
The causative organism, Neisseiria meningitidis, is a Gram-negative bacterium with a polysaccharide capsule. The chemical structure of the capsular polysaccharide determines the serogroup. To date, 13 serogroups have been distinguished, of which A, B, C, W135, X and Y commonly cause invasive human disease. Serogroups A, B and C account for 90 % or more of clinical disease worldwide, although serogroup Y plays an important role in some countries, including the US. Most major outbreaks have been caused by serogroup A strains, particularly within the ‘meningitis belt’ of sub-Saharan Africa (which consists of the countries running from Senegal to Ethiopia), although serogroups C and W135 also play a lesser role. Serogroups B and C have occasionally been associated with outbreaks in the developed world, usually with substantially lower incidence rates than those observed in the meningitis belt. Worldwide, there are around 1.2
© TOUCH BRIEFINGS 2011
million cases of endemic and epidemic meningococcal disease each year, with an estimated 135,000 deaths.1
Humans are the only known
host of N. meningitidis and no animal or environmental reservoirs have been identified.
This increase was associated with the emergence of a highly virulent strain of serogroup C belonging to the sequence type (ST) ST-11 clonal complex. This strain causes severe invasive meningococcal disease and is associated with a high case fatality rate.
Epidemiology of Serogroup C Meningococcal Disease in the Absence of Routine Vaccination In European countries, prior to the widespread use of a vaccine against meningococcal C infection, serogroups B and C predominated as a cause of invasive disease. From the mid-1980s to the early 1990s, a disproportionate increase in the number of cases of meningococcal disease caused by serogroup C was observed in a number of European countries, including England and Wales,2 Republic of Ireland.5
Greece,3 Spain4 and the
In the absence of immunisation, the peak incidence of meningococcal C disease throughout Europe was in children under five years of age with a secondary peak in teenagers between 15 and 19 years of age.6 The rise in serogroup C ST-11 strains was linked to an increase in the proportion of cases observed in teenagers and young adults. This was important as, unlike disease due to meningococcal B infection, the case fatality rates are higher in teenagers between 15 and 19 years of age than in younger children and infants (see Figure 1) and higher in serogroup C disease than serogroup B.7
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