Vaccine-Preventable Diseases

Meningococcal

Guidelines for the Prevention and Control of Meningococcal Disease - Supplement (2005)

More about Invasive Meningococcal Disease

Invasive meningoccocal disease (IMD) is endemic in Canada, and periods of increased activity occur roughly every 10 to 15 years but with no consistent pattern. The last major epidemic of serogroup A meningococcal disease occurred in 1940-43, when the peak incidence was close to 13 per 100,000 population per year. Since then, outbreaks have been uncommon and localized, and the overall incidence of disease has remained at or below 2 per 100,000 per year (range 0.5 to 2.1). The incidence of IMD has varied considerably with different serogroups, age groups, geographic locations and time.  

Serogroups A and C Neisseria meningitidis were the groups most frequently identified from 1971 to 1974. From 1975 to 1989, serogroup B predominated, the majority being serotype 2b, 4 and 15 and the most common subtype P1.2. In 1986, a new clone of serogroup C, serotype 2a, characterized as electrophoretic type 15 (ET-15), was identified in Canada for the first time. Since then serogroups B and C have been responsible for most of the cases of endemic disease in Canada. However, serogroup C isolates have almost exclusively been responsible for clusters or outbreaks in schools and communities.  

Overall, the incidence has been highest among children < 1 year of age and has declined with age, except for a smaller peak in the 15 to 19 year age group. Agespecific incidence rates (per 100,000 population per year) during the period 1985 to 2000 were 14.8 among infants < 1 year old, 4.2 among children 1 to 4 years, 2.3 among those 15 to 19 years and 0.5 among adults >= 20 years. Children < 1 year of age accounted for 18% of cases (mean of 50 cases per year), those 1 to 4 accounted for 21% (mean of 58 cases per year), those 5 to 9 accounted for 7% (mean of 20 cases per year) and adolescents 15 to 19 years of age accounted for 14% (mean of 41 cases per year). One-third of cases occurred in people >= 20 years. The overall case fatality rate (CFR) varied from 9% in 1985 to 12% in 1993 with the emergence of the more virulent ET-15.  

Serogroup C

From January 2000 to June 2001, there has been a resurgence of group C disease with localized clusters or outbreaks, mainly affecting adolescents and young adults, in five provinces (Alberta, British Columbia, Manitoba, Quebec and Ontario). Immunization campaigns, generally targeting high school-aged children and extending to a varying degree to include younger children and young adults, have been launched in different provinces.

Other serogroups

Both serogroup A and W135 IMD are reported uncommonly in Canada. Since the epidemics of the early 1940s the incidence of serogroup A disease has declined dramatically. From 1985 to 2000, a total of 101 cases with invasive serogroup W135 disease were reported (range 1-12 cases per year), with an average incidence of 0.02 per 100,000 population per year (1999 and 2000 data preliminary). The median ages of serogroup A and W135 cases were 18 years and 19 years respectively.  

Meningococcal Vaccine

Efficacy and Immunogenicity

Purified polysaccharide vaccines

These data demonstrate lack of efficacy in those < 2 years, poor efficacy in 2-3 year olds and short duration of efficacy of the serogroup C component of MenAC-Ps and MenACYW-Ps vaccines, particularly in children < 10 years of age.

During a serogroup A epidemic in Africa, the efficacy of polysaccharide vaccines against serogroup A was estimated as 87%. Although protection against serogroup A conferred by MenAC-Ps or MenACYW-Ps vaccine may persist in school-aged children and adults for at least 3 years, the efficacy of the group A vaccine in children aged < 5 years may decrease markedly within this period. In one study, efficacy declined from > 90% to < 10% by 3 years after immunization among children who were aged < 4 years when immunized. Efficacy was 67% at 1 year after immunization among children who were >= 4 years.

Vaccines containing serogroups Y and W135 polysaccharides are safe and immunogenic in adults and in children aged > 2 years, but clinical protection has not been studied after immunization with polysaccharides of these serogroups.

Protein-polysaccharide conjugate vaccines

A high level of protection produced by immunization with MenC conjugate vaccine has been predicted from immunogenicity data, even in infants as young as 2 months. There are limited efficacy data available for MenC-conjugate vaccines. Preliminary data from U.K. surveillance after introduction of the MenC-conjugate vaccine throughout childhood have indicated an estimated short-term (follow-up was approximately 9 months) efficacy of 97% in adolescents and 92% in toddlers.

Recommended Usage

The MenC-conjugate vaccine has been licensed for use in infants, children and adults, and NACI recommends that it be used as follows.

Infants
MenC-conjugate vaccine is recommended for routine immunization of infants at ages 2, 4 and 6 months (normally, at least 4 weeks apart) at the same visit as primary immunization with DTaP, IPV and Hib, to prevent serogroup C meningococcal disease. Infants aged 4-12 months who have not previously received the vaccine shouldbe immunized with two doses given at least 1 month apart.

Infants born prematurely should receive the vaccine at the same chronological age as term infants.

Purified polysaccharide vaccine (MenACYW-Ps or MenAC-Ps) is not recommended for routine infant immunization.

Individuals over 1 year of age

A single dose of MenC-conjugate vaccine is recommended for immunization of children aged 1-4 years and for adolescents and young adults to prevent the increased risk of serogroup C meningococcal disease in these age groups. For children >= 5 years of age who have not reached adolescence, immunization with a single dose of MenC-conjugate vaccine may also be considered.

Purified polysaccharide vaccine (MenACYW-Ps or MenAC-Ps vaccines) is not recommended for routine childhood immunization.

Contacts of cases

Household and intimate social contacts (kissing, sharing a toothbrush etc.) of sporadic cases of meningococcal disease have a considerably elevated risk of infection, and chemoprophylaxis should therefore be administered to them: rifampin 600 mg every 12 hours for 2 days for adults (10 mg/kg in children >= to 1 month of age, 5 mg/kg < 1month); or ciprofloxacin as a single 500 mg oral dose for adults or ceftriaxone 250mg intramuscularly for adults (50 mg/kg in children). Ceftriaxone is recommended in pregnancy and when compliance with oral antibiotics is unlikely. If antibiotics such as penicillin, which do not reliably eliminate nasopharyngeal carriage, have been used for treatment in hospital, before discharge the index case should also receive antibiotics that clear nasal carriage.

In certain countries where chemoprophylaxis of contacts is routinely administered for sporadic cases, as it is in Canada, 0.3% to 3% of cases of meningococcal disease occur in contacts of the index case. In one study, the median interval between occurrence of the index and secondary case was 7 weeks. Some of these secondary cases can be attributed to failure of chemoprophylaxis (e.g., through failure of administration, poor compliance or the presence of antibiotic resistance). The situation in Canada is unknown.

Vaccination of unimmunized household and intimate social contacts may further reduce the risk of secondary cases beyond the benefit of chemoprophylaxis and is recommended. MenACYW-Ps or MenAC-Ps vaccine should be used for contacts of cases with disease known to be caused by serogroup A meningococci; MenACYW-Ps vaccine should be used for contacts of cases of serogroup Y or W135 disease. For contacts of known serogroup C disease, MenC-conjugate vaccine is preferred, when available, because of the longer duration of protection and induction of immunologic memory. However, MenACYW-Ps or MenAC-Ps will also provide useful protection in older children and adults for the 1-year period of increased risk that may follow an epidemic. These polysaccharide vaccines are ineffective against serogroup C disease for children < 2 years of age, and MenC-conjugate should be used in this situation where possible. No vaccine is currently recommended for contacts of individuals with serogroup B disease or contacts of cases of disease in which the serogroup has not been determined.

High-risk groups

Routine immunization with quadrivalent MenACYW-Ps is recommended for certain groups at increased risk of meningococcal disease. Such individuals include those with functional or anatomic asplenia (vaccines should be given at least 10-14 days before splenectomy) and people with complement, properdin or factor D deficiency. More durable protection against serogroup C meningococcal disease may be achieved by giving MenC-conjugate vaccine to these individuals in addition to MenACYW-Ps vaccine. If the MenC-conjugate vaccine is given first, a period of at least 2 weeks before immunization with MenACYW-Ps vaccine is recommended to allow time for generation of an antibody response. It is possible that a shorter interval may interfere with this response. If the MenACYW-Ps vaccine is given first, an adequate response to MenC-conjugate vaccine has been observed after a delay of 6 months in adults, and this remains the recommended interval until further data are available. Children < 2 years with any of these immunodeficiencies should be immunized with MenC-conjugate vaccine as described in the routine infant schedule above, and should then receive quadrivalent MenACYW-Ps at 2 years of age.

Institutions

Routine immunization with the quadrivalent polysaccharide vaccine, MenACYW-Ps, is recommended for military recruits and may be considered for other groups or institutions where there is an increased risk of disease. New guidance on management of outbreaks in institutions is in preparation.

Although there are no data to suggest an increased risk of meningococcal disease among students in Canada living in residential accommodation, an elevation in risk has been observed in the U.S. among freshmen living in dormitory accommodation and in the U.K. among university students in catered hall accommodation. Clusters of cases of meningococcal disease in students have been reported in a number of countries, and carriage rates increase rapidly among freshmen during the first week of term in the U.K. In this age group in Canada, as in other countries, there is an increase in the rate of meningococcal disease. Immunization against serogroup C meningoccocal infection should be considered for students living in residential or dormitory accommodation. For these students the risk is mainly from serogroup C meningococcal disease, and immunization with a single dose of MenACYW-Ps, MenAC-Ps or MenC-conjugate vaccine is appropriate. MenC-conjugate vaccine may be preferred because of the induction of immunologic memory and the enhanced immunogenicity.

Laboratory and health care workers
Clinical health care workers are only at higher risk of meningococcal disease if they are exposed to respiratory secretions from individuals suffering from meningococcal infection around the time of admission. Significant exposure has been defined as intensive, unprotected contact (mask not worn) with infected patients (e.g., through intubation, resuscitation, or close examination of the oropharynx of patients). By 24 hours after antibiotics have been initiated, meningococci are undetectable in the respiratory secretions of patients, and therefore health care workers are at negligible risk.

For the occasional health care staff who have direct exposure to respiratory secretions the relative risk of meningococcal disease is estimated to be 25 times higher than in the general population. It is recommended that health care workers use barrier precautions to avoid direct contact with respiratory secretions of patients with meningococcal disease during the first 24 hours after commencement of antibiotic therapy, and that those with significant exposure receive antibiotic chemoprophylaxis. Routine immunization of health care workers is not currently recommended, as the risk period for acquisition ends when contact with an untreated patient terminates, and antibiotic chemoprophylaxis should be sufficient in the high-risk situation described.

Laboratory-acquired meningococcal infection is believed to be rare. However, the rate of disease in a recent U.S. survey conducted by the Centers for Disease Control and Prevention (CDC), Atlanta, was higher than expected among microbiology laboratory workers dealing with N. meningitidis cultures in the absence of any breaches in laboratory safety practices. In light of this, CDC is currently re-evaluating its recommendations for laboratory workers. Research, industrial and clinical laboratory personnel who are routinely exposed to N. meningitidis should be offered immunization with quadrivalent MenACYW-Ps and may be additionally offered MenC-conjugate vaccine to provide enhanced protection against serogroup C meningococcal infection (see Booster Doses and Re-immunization in the Guide).

Outbreaks of meningococcal disease

Consultation with public health officials and experts in communicable disease is important in the assessment and control of meningococcal disease outbreaks in various settings, and reference to published guidelines (currently being revised) should be made. Most recent outbreaks of meningococcal disease in Canada have involved teenagers and young adults suffering from serogroup C meningococcal disease. Such outbreaks may be controlled by the use of MenACYW-Ps, MenAC-Ps vaccine or MenC-conjugate vaccine. The use of MenC-conjugate vaccine may be preferable because of induction of immunologic memory and prolonged duration of protection. In those previously immunized with a polysaccharide vaccine for whom re-vaccination is considered, MenC-conjugate vaccine is preferred (see Booster Doses and Reimmunization), as further plain polysaccharide immunization may induce immunologic hyporesponsiveness, although the clinical significance of this phenomenon is unknown. In younger children (< 10 years) MenC-conjugate vaccine is recommended for control of outbreaks in view of its superior immunogenicity and efficacy in this age group.

For the control of outbreaks of serogroup A meningococcal disease, MenACYW-Ps or MenAC-Ps vaccine is recommended as a single dose for children > 18 months of age and adults. Children aged 3 to 17 months should receive two doses of vaccine given 3 months apart. For the control of outbreaks associated with serogroup Y or W135 meningococci, one dose of MenACYW-Ps is recommended for people >= 2 years.

International travel

Current Canadian guidelines (from the Committee to Advise on Tropical Medicine and Travel) for the prevention of meningococcal disease in travellers should be consulted. In deciding on the need for immunization, there should be particular consideration of the destination to be visited, the nature and duration of exposure, and the age and health of the traveller.

Epidemic alerts are published regularly on the following websites:

Travel Medicine Program,
Centre for Emergency Preparedness and Response
Health Canada

U.S. Centers for Disease Control and Prevention (CDC)

World Health Organization (WHO)

Immunization of travellers to areas known to have epidemic meningococcal disease generally aims to prevent serogroup A infection. Epidemics of serogroup A meningococcal disease have been documented every 5 to 10 years in the meningitis belt of sub-Saharan Africa for much of the past century. A similar epidemic pattern has also been described in Asia. Despite the frequency of travel to regions where meningococcal epidemics occur, disease in travellers appears to be very unusual. When vaccine is indicated, a single dose of MenACYW-Ps or MenAC-Ps vaccine should be given to infants >= 3 months, children, adolescents and adults to prevent serogroup A meningococcal infection.

Large outbreaks of meningococcal disease have affected pilgrims travelling to, and returning from, Mecca, Saudi Arabia, involving serogroup A in 1987, and both serogroup A and W135 in 2000 and 2001. Pilgrims making the annual Hajj pilgrimage to Mecca should receive a single dose of MenACYW-Ps vaccine at least 2 weeks before departure. MenC-conjugate vaccine alone is not appropriate as it does not protect against outbreaks of serogroup W135 or epidemics of serogroup A disease.

Route of Administration and Dosage

MenAC-Ps and MenACYW-Ps vaccines are given as a single 0.5 mL subcutaneous injection to children > 2 years and adults at a separate anatomic site from other coadministered vaccines. For specific protection against serogroup A meningococcal disease this vaccine may be given from 3 months of age.

MenC-conjugate vaccine is given as a single 0.5 mL dose to people > 1 year of age by intramuscular injection. For infants, three doses are given at 2, 4 and 6 months at the same time as the routine primary series, administered at a separate site with a different syringe. Two doses are offered to infants from 4 to 12 months of age who missed the first dose. The minimum interval between doses is normally 4 weeks. The vaccine should preferably be administered in the anterolateral thigh in infants and in the deltoid region in older children and adults.

Booster Doses and Re-immunization

The need for, or effectiveness of, re-immunization with meningococcal polysaccharide vaccine has not been fully established. Repeated immunization may induce immunologic hyporesponsiveness to polysaccharide vaccines, although the clinical significance of this phenomenon is unknown. Re-immunization should be considered, according to the Table, for those continuously or repeatedly exposed to serogroup A disease who have been previously immunized with MenACYW-Ps or MenAC-Ps, particularly for children initially immunized at < 5 years of age. Children or adults with immunodeficiencies resulting in increased risk of meningococcal disease caused by serogroup A, C, Y or W135 meningococci may be re-immunized with MenACYW-Ps according to the Table.

The new MenC-conjugate vaccine is believed to induce immunologic memory that can be demonstrated for at least 5 years after primary immunization. Re-immunization with MenC-conjugate vaccine is not thought to be necessary at present, although there are insufficient data to predict persistence of immunologic memory (and presumed protection) beyond 5 years. Individuals who have previously received MenACYW-Ps or MenAC-Ps may receive MenC-conjugate vaccine for continued protection against serogroup C meningococcal disease after primary immunization.

Since an adequate response to MenC-conjugate vaccine has been observed with a delay of 6 months after immunization with purified polysaccharide vaccine in adults, this remains the recommended interval until further data are available. In other circumstances, when MenC conjugate vaccine has already been administered and protection against serogroup A, Y or W135 meningococci is required, a period of 2 weeks should elapse before immunization with MenACYW-Ps to allow time for generation of an antibody response and avoid possible interference with this response by the polysaccharide vaccine.

Storage and Handling Requirements

All of the available products should be stored at a temperature between 2° C and 8° C and must not be frozen. The vaccines should be reconstituted immediately before use according to the manufacturer's instructions.

Simultaneous Administration with Other Vaccines

Administration of MenC-conjugate vaccine at the same time as, but at a separate injection site from, IPV, DTP, Hib, DTaP, DT, Td and MMR vaccines or OPV does not reduce the immunologic response to any of these other antigens. In a study in Canada, there was no interference noted with PentacelTM antigens.

There is no information on co-administration of MenC-conjugate vaccine with hepatitis B vaccines.

Adverse Reactions

Purified polysaccharide vaccines

Both MenACYW-Ps and MenAC-Ps vaccines have been used extensively in many countries for mass immunization programs and to immunize military recruits, people who are immunocompromised and travellers. Mild reactions to the vaccines include pain and redness at the injection site in up to 50% and transient fever in 5%, particularly infants. Severe reactions to these vaccines are very unusual but include systemic allergic reactions (urticaria, wheezing, and rash) in >= 0.1/100,000 doses, anaphylaxis in < 1 per million doses and occasional neurologic reactions. These vaccines have an established safety record.

No adverse events have been documented during pregnancy or in newborn infants of immunized mothers.

Protein-polysaccharide conjugate vaccines

Safety and adverse event data are available from a number of clinical trials of MenC-conjugate vaccine and MenAC-conjugate vaccine in addition to accumulated data from spontaneous reporting on 12 million doses distributed in the United Kingdom in 1999-2000. Mild reactions were reported as follows: local reactions (redness, tenderness, and swelling at the injection site) in up to 50% of vaccinees, irritability in up to 80% of infants and fever > 38o C in up to 9%when other vaccines were administered. These mild reactions occurred at a lower rate than that produced by other childhood immunizations or other purified polysaccharide vaccines.

Headaches and malaise occured in up to 10% of older children and adults. There may be some variation among the three MenC conjugate vaccines in terms of adverse reactions, although one U.K. study found no significant differences in a comparison of the three MenC-conjugate vaccine products in toddlers.

In one Canadian study, MenC-conjugate vaccine (MenjugateT) was administered with PentacelT (DTaP/Hib/IPV) in a multi-centre, randomized controlled clinical study involving three centres that compared MenC conjugate vaccine with hepatitis B vaccine (HBV). The frequency of local adverse reactions (tenderness, erythema and induration) among those receiving MenC conjugate vaccine was lower than among those receiving routine infant immunization with PentacelT, but higher than among those receiving HBV, a vaccine used in a number of provinces for infant immunization. Systemic reactions were experienced at the same rate in those receiving HBV as those receiving MenC-conjugate vaccine.

The frequencies of rare adverse events are based on spontaneous reporting rates from the United Kingdom and have been calculated using the number of reports received as the numerator and the total number of doses distributed as the denominator. Severe reactions were very uncommon and included systemic allergic reactions (lymphadenopathy, anaphylaxis and hypersensitivity reactions, including bronchospasm, facial edema and angioedema) in < 0.01%; neurologic responses (dizziness and convulsions, including febrile convulsions, faints, hypesthesia, paresthesia and hypotonia) in < 0.01%; nausea or vomiting in < 0.01%; rash, urticaria or pruritis in 0.01%; and arthralgia in < 0.01%. No deaths in the United Kingdom have been attributed to this vaccine.

There are no specific studies in humans of MenC-conjugate vaccine during pregnancy or lactation.

Contraindications

Both purified polysaccharide vaccines and the new protein-polysaccharide conjugate vaccine are contraindicated in people with a known hypersensitivity to any component of the vaccine and in those who have shown signs of hypersensitivity after previous administration of the vaccine (see Anaphylaxis section, part I of the Guide).

Precautions

The new MenC-conjugate vaccine will not protect against meningococcal diseases caused by any of the other types of meningococcal bacteria (A, B, 29e, H, I, K, L, W135, X, Y, or Z, including non-typed). Complete protection against meningococcal serogroup C infection cannot be guaranteed. Conjugate vaccines containing CRM197 or tetanus toxoid should not be considered as immunizing agents against diphtheria or tetanus. No changes in the schedule for administering vaccines containing diphtheria or tetanus toxoids are recommended.

MenACYW-Ps and MenAC-Ps vaccines do not provide any cross-protection to meningococci not contained in these vaccines and do not provide complete protection against the vaccine serogroups.

MenC-conjugate has not been studied in pregnancy, and the vaccine should not be used unless there are specific circumstances in which the benefits outweigh the risks.

Other Considerations

The studies described here have clearly demonstrated that MenC-conjugate vaccine can induce immunologic memory for at least 5 years after primary immunization. However, protection is important beyond early childhood even more so than is the case with Hib vaccine. It is currently unknown whether there is a need for a booster dose at some point after infancy to provide protection through adolescence and early adulthood, and this requires close monitoring and further investigation. The ability of MenC-conjugate vaccine to induce herd immunity is unknown.

Based on bactericidal antibody levels at 1 month after immunization it is possible that two doses of MenC-conjugate vaccine in the first 6 months of life may be sufficient. Further data are required on the duration of protective levels of bactericidal antibody following different immunization regimes before this can be recommended. Although use of MenC-conjugate vaccine probably provides superior protection against serogroup C meningococcal disease than MenC-polysaccharide vaccines, there are no data available on its use in immunodeficient subjects. There are no safety or immunogenicity data available regarding the use of MenC-conjugate vaccine in adults aged > 65 years; no data on the use of the vaccine in outbreak control; and no formal studies of its use in pregnancy or lactation.

The effect of MenC-conjugate vaccine on meningococcal population biology is unknown. It has been suggested that use of a monovalent meningococcal vaccine might induce capsule switching through immunologic pressure, such that hypervirulent serogroup C clones adopt a B, Y or W135 capsule. It may also be the case that use of a monovalent vaccine will have little overall effect on meningococcal disease burden if other meningococci simply replace the niche left by serogroup C meningococci (strain replacement). After the introduction of widespread meningococcal immunization, close epidemiologic and laboratory-based surveillance must be undertaken to monitor changes in meningococcal population biology.

Cost-effectiveness data and information on parental attitudes to immunization are not currently available but would help guide use of meningococcal vaccines in routine immunization in Canada. The merits of MenC-conjugate vaccine relative to other vaccines (e.g., pneumococcal protein polysaccharide conjugate vaccines, adult pertussis vaccine and varicella vaccine) have not been fully studied yet.

New quadrivalent protein-polysaccharide conjugate vaccines (MenACYW-Con) are in development and might provide broad protection against the vaccine serogroups after introduction of an infant immunization program; they could presumably replace monovalent MenC-conjugate vaccines. None of these vaccines offers protection against serogroup B meningococci, a feature that limits the impact that any meningococcal vaccine can have on the disease burden, especially in children.

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