MeNZB™ epidemic vaccine programme endsRoutine MeNZB™ immunisation for children under 5 years old finished 1st June 2008. The epidemic has now waned to the point where vaccination can be discontinued. It is recommended that those who started a course do finish all their doses and vaccine will still be available (and recommended) for individuals at higher risk of disease, such as laboratory workers and those without a spleen. MeNZB™ continues to be available for those less than 20 years old who are concerned and the doctor considers they are at risk. There will still be cases of both meningococcal B and other forms of meningococcal disease that continue to occur, likely for many years to come. Parents and health professionals will have to remain vigilant for the worrying signs in unwell children. Seek medical help immediately if concerned. More information on the cessation of the vaccine can be found here: - Causative Organism
- Clinical Signs, Symptoms and Complications
- Method of Transmission
- Public Health Significance
- Prevention
- Vaccine
- Efficacy and Effectiveness
- Dosage and Administration
- Indications and Recommendations
- Contraindications
- Adverse Events
- Risks vs Benefits
Causative OrganismBacteria from the family Neisseria meningitides causes meningococcal disease. The bacterium has a “slimy” polysaccharide coating to which the infant immune system does not respond well prior to the age of two years. There are 13 serologically distinct groups defined on the basis of the capsular polysaccharide but the serogroups that most commonly cause disease are A, B, C, Y and W-135. Signs, Symptoms and Complications- Infection usually results in septicaemia and/or meningitis.
- The illness occurs quickly with fevers, chills, collapse and sometimes a rash.
- Deterioration of the patient is rapid and haemorrhage, shock, coma and death can occur within several hours despite antibiotic therapy.
- Other localised infections can occur but are uncommon; these include: arthritis, myocarditis, pericarditis, endophthalmitis or pneumonia.
- Sensorineural deafness occurs in patients with meningococcal meningitis. Gangrene, secondary to septicaemia, usually leads to limb amputation (5-20%).
Method of Transmission- Around 10% of people carry the bacteria in their nose and throat without it causing infection.
- It is spread from person to person through droplets (coughing or sneezing) or direct contact with respiratory secretions.
Public Health Significance- Meningococcal disease is a global problem that occurs in all countries.
- Meningococcal disease can occur in short, violent outbreaks (particularly A), longer lasting epidemics (e.g. B) and even longer term endemic rates (e.g. C, and B).
- As with most respiratory disease it is often worst in situations of overcrowding.
- The highest rates of disease occur in infants, although during outbreaks among adolescents and young adults high rates may be seen.
- People with asplenia have an increased risk of meningococcal infection.
- In countries with developed economies, the case fatality rate is 4-10%.
There are significant sequelae: - Sensorineural deafness and limb amputation occur in 5-20% of cases.
- 25% will have long-term behavioural and learning difficulties.
- Group A is the major cause of endemic meningococcal diseases in the commonly termed ‘meningitis belt’ of Sub-Saharan Africa. The annual incidence can on occasions exceed 1000 per 100, 000 population with a case fatality rate of 10 –15%.
- Protection from Group A and W135 need to be considered for all travellers to this area, including all Hajj pilgrims in whom vaccination is a requirement.
Epidemics of serogroup B disease have been reported in Norway, Cuba, Brazil, Chile and NZ. - Groups C and Y cause outbreaks among tertiary and high school students in most countries with developed economies.
New Zealand epidemiology (From the 2006 New Zealand Immunisation Handbook) - In 2008 the rates of cases of meningococcal B epidemic strain disease in New Zealand reduced to the point where the routine immunisation programme has been discontinued.
- Since 1991 there has been a persistently elevated rate of meningococcal disease in New Zealand, increasing from 53 cases recorded in 1990 to a peak of 648 cases in 2001.
- Since 2001 there has been a gradual decline in the number of cases reported, with 344 cases reported in 2004. This annual rate in 2004 was 9.2 cases per 100,000, compared with the rate of 1.5 per 100,000 in the non-epidemic years 1989/90 and a rate of 17.4 per 100,000 in 2001.
- Historically, in New Zealand the dominant serogroup has been serogroup B, except for a large outbreak of serogroup A in Auckland in 1985/86, and small group C outbreaks in south Wellington and Taranaki during 1994, Otago in 2002 and 2003, and Huntly in 2005.
- A mass immunisation programme using a group A polysaccharide vaccine controlled the group A outbreak in Auckland.
- In response to the group C outbreaks, quadrivalent vaccine was given to geographically defined populations two to four years of age in Wellington, and two to nine years of age in Taranaki.
- In response to the Otago outbreaks, staff and school students were given quadrivalent polysaccharide vaccine in one outbreak, and students in hostel accommodation were offered the quadrivalent vaccine in the second outbreak.
- The meningococcal conjugate group C vaccine was offered to school students in the Huntly outbreak in 2005.
- The proportion of isolates from N. meningitidis serogroup B disease rose from 47.8 percent in 1990 to 88.4 percent (282 out of 319 isolates) in 2001, and 87.3 percent (220 of 252 isolates) in 2004.
- The increase in disease rate in all years is mostly from the epidemic strain B:4:P1.7b,4.
- In 2001, 262 of the 319 isolates (88.4 percent) and in 2004, 184 of the 252 isolates (73 percent) were of this sero-subtype.
- During this epidemic, disease rates have been higher in the winter months and consistently higher in Auckland and the northern region of New Zealand.
- The rate of disease in 2004 was 11.6 per 100,000 total population in the northern region compared with 9.7 per 100,000 in the midland region, and 7.0 per 100,000 in both the central and southern regions.
- In 2004, 273 of the 342 total cases (79.8 percent) were laboratory confirmed cases, with the remainder diagnosed on clinical grounds.
- Rates of disease are highest in infants under one year of age, and in children between one to four years of age.
- Rates are consistently higher in Maori and Pacific children compared with the total population.
- The rate in 2004 for Maori children one to four years of age was 85.9 per 100,000 and in Pacific children 93.9 per 100,000, compared with the total population rate of 44.4 per 100,000 for children one to four years of age.
- Similar increases of a lesser magnitude of serogroup B disease have been reported by other comparable countries, including Norway, the Netherlands, Oregon (US) and the UK.
Preventioni) Non-immunisation related preventions - Public health initiatives that reduce smoking, overcrowding, poverty and poor nutrition may help reduce the incidence of disease.
- Prompt identification and treatment of cases reduce the fatality rate. Close contacts should be treated with appropriate antibiotics aims to reduce the spread of the organism.
ii) Vaccination - Polysaccharide meningococcal vaccines available as monovalent A, bivalent A, C and quadrivalent A, C, Y and W-135 are used in the control of epidemics.
- Quadrivalent A,C,Y,W135 Polysaccharide vaccine is used for individual protection for travellers.
- Polysaccharide vaccines however, have limited efficacy for children under the age of two years and do not include B serotype.
- Group C Conjugate vaccines, which are effective at preventing disease in children under two as well as older age groups, are now becoming available on some national immunisation schedules for prevention of disease cause by group C meningococci.
- A quadravalent conjugate (A, C, Y, W135) has recently (2005) been licensed in the US for 11-55 year olds, and is likely to be more widely available in the future. Safety and efficacy are not yet established for those aged <11 or >55 years.
- Some Countries with epidemics of group B disease have developed strain-specific outer membrane protein vaccines to control epidemics of group B meningococcal disease though these vaccines are not generally commercially available. An OMP-based vaccine was used in NZ. Several companies are developing vaccines against group B meningococci and it is possible such vaccines may be commercially available in the future.
Vaccine- Polysaccharide and Group C conjugate vaccines are widely available in most countries with developed economies.
- A serogroup-specific quadrivalent vaccine consisting of each of the respective (A, C, Y & W135) purified bacterial capsular polysaccharides.
- The Meningococcal C polysaccharide antigen is chemically linked (i.e. conjugated) to a carrier protein.
- A quadravalent conjugate vaccine consisting of group A, C, Y and W135 capsular polysaccharide chemically linked to diphtheria toxoid has recently been licensed in the USA.
- New Zealand's MeNZB™ vaccine, specifically developed to address the Group B epidemic is no longer routinely offered.
Efficacy and EffectivenessPolysaccharide - Polysaccharide vaccines are poorly immunogenic in children under 2 years of age. The exception is group A polysaccharide which is immunogenic in a two dose schedule, 3 months apart from 3 months of age. It has been used in this age group for epidemic control.
- These vaccines induce antibodies in 90% of recipients over the age of 2 years after a single dose. Immunity decreases markedly during the first 3 years following a single dose, particularly for children immunised under 5 years of age.
- Some countries with developed economies recommend re-vaccination after 5 years to those at continued risk but there is no standardisation.
- It is possible that the ACYW135 protein conjugate vaccine may replace the polysaccharide vaccine for most age groups.
Conjugate Meningococcal C - Conjugate vaccines are highly immunogenic in children under 2 years of age.
- 95% of infants under 6 months of age demonstrate a protective immune response when given a two or three dose series.
- In children over 12 months of age a single dose appears sufficient to induce protective antibody responses.
- The duration of immunity is currently unknown. Manufacturers do not currently provide a recommended booster schedule, however a booster dose following the primary course in infants may be needed to sustain longer-term immunity.
- Highly immunogenic in adolescents with 82-97% achieving a greater that 4-fold rise in antibody titres against all 4 groups.
OMP/OMV Group B vaccines Efficacy - The two most evaluated OMP vaccines are those produced in Norway in response to an epidemic with the strain B:15:P1.7.16, and a vaccine produced in Cuba in response to a B:4:P1.19.15 strain epidemic.
- The Norwegian vaccine was given in a randomised controlled trial as two doses to 13 to 14 year old school children and showed an efficacy of 57 percent at 29 months. A later evaluation estimated that the vaccine efficacy at 10 months after the introduction of the vaccine was 87 percent.
- The vaccine was not introduced nationally because the epidemic declined and the efficacy of 57 percent was judged insufficient.
- The Cuban vaccine, a combined group C polysaccharide vaccine with the group B OMP vaccine, had an efficacy of around 80 percent in a randomised trial among adolescents.
- Vaccination of all Cubans under 20 years of age, and ongoing routine vaccination of all infants with two doses of the vaccine, had contributed to the continuing control of the disease in Cuba.
- The Cuban vaccine was also used in mass immunisation campaigns in some Latin American countries experiencing outbreaks of meningococcal group B disease caused by varying proportions of the same strain as Cuba.
- Two doses of the Cuban vaccine were effective in older children, but in children under four years of age results varied from showing no effect to a moderate effect. However, it was observed that if vaccination led to a rise in serum bactericidal antibody levels this was suggestive of vaccine efficacy. Vaccine efficacy appeared to be higher when the vaccine strain was similar to the outbreak strain.
- A study in Chile, using both the Norwegian and the Cuban vaccines, compared the antibody response in infants, children and adults. Following three doses, over 95 percent of infants sustained a four-fold rise in serum bactericidal antibody against the vaccine strains.
- This suggests that three doses of an OMV vaccine could provide clinical protection in this age group.
- Based on the known efficacy of these other OMV vaccines and the known corrolates of protection it was decided not to carry out efficacy trials for the MeNZB™ vaccine. This would have delayed the availability of the vaccine by several years to a population experiencing an epidemic.
Effectiveness of MeNZB™ - Data on the effectiveness of the MeNZB™ vaccine is emerging as the programme comes to a conclusion. the data suggest the vaccine is around 73% effective.
- The immunisation programme began in the northern region in the second half of 2004. In 2005 and 2006 to date there has been a dramatic decrease in cases of the epidemic strain of meningococcal disease in this region.
- There were 20 cases of epidemic strain meningococcal disease in 6 week to 19 year olds reported from the northern region in 2005 compared with 61 cases in 2004 and 84 cases in 2003.
- In 2006, there have been five cases reported to the end of May, which is similar to the pattern seen in 2005.
- Meningococcal epidemics typically have peaks and troughs but since the introduction of the vaccine we are seeing a sharp reduction in case numbers.
- The immunisation programme began in the northern region in the second half of 2004. In 2005 and 2006 to date we have seen a dramatic decrease in cases of the epidemic strain of meningococcal disease in this region.
- There were 20 cases of epidemic strain meningococcal disease in 6 week to 19 year olds reported from the northern region in 2005 compared with 61 cases in 2004 and 84 cases in 2003.
- In 2006, there have been five cases reported to the end of May, which is similar to the pattern seen in 2005.
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| Graph courtesy of Ministry of Health |
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- The immunisation programme began in the rest of New Zealand (outside the northern region) in 2005. While there has been a decrease in epidemic strain cases in these regions each year since 2002, there is a much larger decrease in cases in 2006 than expected, which suggests a vaccine effect.
- There have been six cases of epidemic strain reported in 6 week to 19 year olds in the rest of New Zealand to the end of May this year. This compares with 31 at the same time in 2005 and 28 in 2004.
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| Graph courtesy Ministry of Health |
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- As vaccine coverage has increased there has been a corresponding decrease in epidemic strain meningococcal disease cases. By May 2006, 83% of children aged 6 weeks to 19 years living in the northern region had received three doses of MeNZB™.
- There was no apparent winter peak in cases, which typically occurs in July/August, in the northern region in 2005.
- To date there have been 13 cases of epidemic strain meningococcal disease in children who have had three doses of MeNZB™ in the northern region.
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| Graph Courtesy Ministry of Health |
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- By May 2006, 77% of children aged 6 weeks to 19 years living in the rest of New Zealand (outside the northern region) had received three doses of MeNZB™.
- There have been three cases of epidemic strain meningococcal disease in children who have had three doses of MeNZB™.
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| Graph courtesy of the Ministry of Health |
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Administration - Subcutaneous injection for polysaccharide
- Conjugate vaccines are administered intramuscularly
Indications and Recommendations
Polysaccharide - Routine immunisation of children with these vaccines is not recommended.
- Epidemic control recommendations are formed locally.
- Travellers to endemic areas (e.g. Sub-Saharan Africa) should consider meningococcal polysaccharide vaccine.
- Hajj pilgrims to Mecca, Saudi Arabia usually require proof of vaccination before arrival in the country.
- Lab workers exposed to meningococci may be offered vaccine by their employers. However this is not a replacement for standard laboratory practices.
- Immunosuppressed individuals should be offered vaccination (actual or functional asplenia, sickle cell anaemia, complement deficiencies, HIV).
- This vaccine could be considered for tertiary students entering halls of residence – see also below.
Conjugate Meningococcal C - Primary immunisation for young infants is commonly 3 doses at age 2, 4 and 6 months.
- Children age 12 months and over require one dose.
- In some countries with developed economies, this vaccine is part of their routine schedule and some are using it selectively to control local outbreaks or epidemics.
- Some countries with developed economies (e.g. some states in the US) recommend tertiary students living in halls of residence consider meningococcal C conjugate vaccine (or the quadravalent conjugate A, C, Y, W135).
- Lab workers exposed to the disease (in addition to standard handling protocol).
- Immunosuppressed individuals (actual or functional asplenia, sickle cell anaemia, complement deficiencies, HIV).
Quadravalent Conjugate
11-55 year olds single 0.5ml dose ContraindicationsPolysaccharide - Those with previous anaphylactic reaction to the vaccine or any of its components.
- Pregnant women should only be immunised if they have substantial risk of infection.
Conjugate Meningococcal C - Those with previous anaphylactic reaction to the vaccine or any of its components.
- The vaccine has not been adequately assessed in elderly patients over 65 years.
Quadravalent Conjugate - Those with previous anaphylactic reaction to the vaccine or any of its components and natural rubber latex.
Adverse reactionsPolysaccharide
Local reactions are usually mild and infrequent include redness, swelling and pain at the injection site and local axillary lymphadenopathy.
Fever and chills occur in approximately 2% of young children. Significant reactions are rare.
Conjugate
Common reactions are pain, redness and swelling at the site of injection, fever irritability, anorexia and headaches. Systemic reactions tend to decrease with increasing age; local adverse events tend to increase with increasing age. Serious general adverse events are rare.
Quadravalent Conjugate
Local reactions similar to those following tetanus and diphtheria (Td) vaccine.
Generally mild and consist mainly of pain, redness and induration at injection site, headache, fatigue and malaise. These are all of short duration.
OMP-based vaccines
Strain specific outer membrane protein vaccines have been used selectively to control epidemics of a particular strain of serogroup B disease e.g. New Zealand, Cuba. Schedules vary according to vaccine and age group. Schedules have been used for 2, 3 and 4 doses.
Contraindications include anaphylaxis to a prior dose of vaccine or to a vaccine component.
These vaccines cause frequent injection site reactions and transient systemic upset but have an excellent safety profile.
- There has been a decrease in epidemic strain meningococcal disease cases among 6 week to 19 year olds in all ethnic groups in the northern region.
- The greatest effect is seen among Maori where the rate has decreased by 90% in 2005 compared with 2003. The rate among Pacific children has decreased by 70% over the same time period.
Risks vs Benefits (polysaccharide and conjugate vaccines) Disease | Risk from disease | Risk from vaccination | Meningococcal disease – a rapidly progressing, often fatal infectious disease that causes meningitis and septicaemia. | Case fatality 10 - 15% Severe scarring or loss of limbs secondary to septicaemia 3-5% Brain damage including sensorineural deafness and ongoing behavioural and learning difficulties 3-5% Epilepsy. | Conjugate vaccine: mild local or systemic reaction 10% Anaphylactic reactions <0.01% Polysaccharide vaccine: mild local or systemic reaction 3-5% Anaphylactic reactions<0.01% Neurological reactions 0.5 per 100,000 vaccinees
OMP Vaccines: Common transient local reactions in vaccinees. |
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| Graph courtesy of the Ministry of Health |
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