13. Meningococcal disease

Incidence and serotypes

The prevalence of meningococcal groups varies geographically. The highest burden of disease occurs in sub-Saharan Africa, where despite a dramatic fall in Group A disease following introduction of a Group A conjugate vaccine, in this ‘meningitis belt’ epidemics continue with around 30,000 cases reported annually, now including Group W.

The incidence in Canada, the US and Europe varies substantially from 0.2 to 3 per 100,000 persons per year.[3] Group B has become the predominant capsular group in Europe, Americas and Australia, with incidence typically highest in children aged under 2 years.[4] Group C disease has almost disappeared in countries with universal immunisation programmes, but outbreaks have been observed in men who have sex with men in the US and Europe.

Since 2009 there has been an emerging global incidence of Group W disease, initially in the United Kingdom and South America. Australia has experienced a rapid increase in Group W cases since 2013 with New Zealand also seeing a rapid increase in cases since 2017. Like group C clonal complex ST11 strains, group W ST11 strains have enhanced virulence. Higher rates of carriage of these ST11 strains has been noted within age groups where invasive group W disease is more prevalent (infants and the elderly).[5]

Some parts of the world, particularly Scandinavia, have reported an increase in group Y disease. In other regions, there is evidence of colonisation, but disease caused by group Y is rare. Patients with group Y strain disease are more likely to develop pneumonia and to be elderly.[3, 4]

This emergence of group W and Y strains has led to meningococcal C vaccines being replaced by quadrivalent (group A, C, W, Y) meningococcal conjugate vaccines (MenACWY).

Risk groups

The highest incidence of meningococcal disease occurs in children aged under 5 years (especially under 2 years) with a secondary peak in older adolescents (15–19 years).The age distribution for groups W and Y is more likely to include older people that for B and C. A pooled overall case-fatality rate of 8.3 percent (range 4.1–20 percent) is reported internationally, varying by group and age.[6]

Most infection occurs in healthy people, but those with certain rare immune deficiencies (of terminal components of complement (C5–9) or properdin) or asplenia are at much higher risk, particularly of recurrent meningococcal disease. Individuals with infection caused by groups other than A, B, C, W, Y and untypeable strains or who experience recurrent disease should be investigated.

Close contacts of primary cases of meningococcal infection are at increased risk of developing infection, such as the case’s household,[7] early childhood education services, semi-closed communities, schools, correctional facilities and military recruit camps. Students living in hostel accommodation may also be at higher risk.[8, 9, 10] In health care settings, only those with close exposure to oropharyngeal secretions of patients with meningococcal disease (as may occur during intubation or resuscitation) and microbiology laboratory workers are considered to be at increased risk.

It is not possible to calculate the incubation period for meningococcal disease for sporadic cases. Secondary cases (ie, in contacts of known cases of meningococcal disease) usually occur within four days, but it can be up to 10 days. The infectivity of patients with meningococcal disease is markedly reduced after 24 hours of antibiotic therapy, although treatment with cefotaxime, ceftriaxone, rifampicin or ciprofloxacin is necessary to reliably eradicate nasopharyngeal carriage (see section 13.8.2).

In high-income countries in the absence of immunisation, nasopharyngeal carriage of N. meningitidis occurs in approximately 10 percent of the overall population, rising from 2 percent in children aged under 4 years to a peak of 24.5 percent to 32 percent among 15–24-year-olds, then declining with increasing age.[3, 11] In adolescents and young adults, the overall and capsular group carriage vary between regions and age groups.[12] The relationship between risk factors for disease and those associated with carriage is incompletely understood.[3] Carriage prevalence does not predict the disease incidence nor the occurrence or severity of outbreaks, as most of the carried strains are non-encapsulated and do not cause disease.[3] Smoking, passive smoking, household crowding and upper respiratory tract infections increase carriage.

Incidence and mortality

In 2021 the notification rate for meningococcal disease was 0.9 cases per 100,000 population, with a total of 44 cases notified (40 laboratory confirmed; ESR, 28 April 2022). Cases remained significantly lower than the peak annual incidence rate of 16.7 per 100,000 for all ages and 200 per 100,000 in children under 12 months as experienced in 2001 during the meningococcal epidemic from 1991 to 2007. The epidemic was largely due to a single Group B subtype (B:P1.7-2,4). The annual number of notified cases of meningococcal disease in New Zealand since 1970 is shown in Figure 13.1.

For further details and reports of meningococcal disease in New Zealand refer to the ESR surveillance reports.

Figure 13.1: Notified cases of meningococcal disease, 1970–2021

Figure 13.2: Meningococcal disease notifications by group, 2014–2022 (provisional data for 2022)

Internationally, meningococcal vaccination programmes were revolutionised by the development of conjugate vaccines, which allow vaccination in younger children and induced herd immunity when used in population-wide programmes due to reduced nasopharyngeal carriage (see section 1.4.3).

The monovalent (C) and quadrivalent (ACWY) conjugate vaccines are conjugated to a protein, either CRM197 (diphtheria toxin-derived), diphtheria toxoid or tetanus toxoid. Previously used, polysaccharide-only vaccines provided three to five years’ protection in adults, but they are generally regarded as inferior to conjugate vaccines and are no longer approved for use in New Zealand. Those travelling to Africa, the Middle East and other areas with wide serogroup prevalence, including group A, require MenACWY vaccine for broad protection. In 2018, a multicomponent meningococcal group B recombinant vaccine (MenB, formerly abbreviated 4CMenB) was registered in New Zealand to protect against group B disease.

With the current New Zealand epidemiology, neither MenACWY nor MenB give protection across all prevailing meningococcal groups and both types of vaccine are recommended. The meningococcal vaccines registered and available are summarised in Table 13.3 below.

Meningococcal group B recombinant vaccine

Three years after initiation of the introduction of MenB to the national immunisation schedule in the UK, a 75 percent reduction in group B disease was reported in the vaccine-eligible age groups compared with a historical cohort.[15] With 88 percent coverage but a low number of cases (25), adjusted vaccine effectiveness for all group B strains was 59.1 percent (95% CI: -31.1–87.2) following two primary doses and one booster dose, with an estimated 277 cases prevented.[15] This research is ongoing.

Following MenB vaccination of adolescents aged 15-16 years in South Australian schools, there was an overall reduction of 71 percent (95% CI 15-90; p=0.02) in group B meningococcal disease cases aged 16–19 years: five cases in 2017–2018 (predicted 9.9 [95% predicted interval 3.9-17.5]) and one case in 2018–2019 (predicted 10.9 [4.4–19.1]).[16]

As was observed during college outbreaks in the US,[17, 18] in South Australia where MenB is administered in a school-based programme at age 15–18 years, MenB had no effect on disease-causing meningococcal carriage suggesting that vaccination of adolescents is unlikely to generate herd immunity.[19] A MenB vaccination campaign used during an isolated outbreak in a region of Québec, Canada outbreak demonstrated direct protection of 79 percent against outbreak strain group B disease and an overall impact of 86 percent in target groups with no herd effects.[20]

Cross-protection against meningococcal group W has been observed following vaccination of infants with MenB in the UK. Among age-cohorts that were fully and partially eligible to receive MenB, respectively, it was estimated that there were 69 percent (adjusted incidence rate ratio 0.31; 95% CI 0.2-0.67) and 52 percent (0.48; 0.28-0.81) fewer cases of group W disease than predicted in 2018/2019; this included direct and indirect protection over four years. An estimated 98 cases (95% CI 34-201) of group W disease were directly prevented in children aged under 5 years.[21] The researchers state that MenACWY conjugate vaccines would still be required for direct and indirect protection against those groups, since the degree of cross-protection is dependent on the expression of vaccine antigens on the meningococcal surface.[21]

There is limited data on its use in patients with chronic medical conditions and those immunocompromised by medication or disease, such as HIV infection or hereditary immune system defects. In a phase 3 clinical trial, children aged 2­–17 years showed good but reduced immunogenicity in those with immunocompromise.[22] Immunogenicity in children with asplenia and splenic dysfunction was similar to healthy children but reduced in children with complement deficiencies.[23]

The safety and efficacy of MenB in adults above 50 years of age have not been established.

Quadrivalent meningococcal conjugate vaccines

Clinical trial data use immunogenicity and bactericidal antibody titres as a proxy for efficacy. Effectiveness of conjugate meningococcal vaccination against laboratory-confirmed disease is difficult to assess due to the low incidence of cases, even during localised epidemics, such that data is limited around the effectiveness of the MenACWY vaccines. With the emergence of group W and Y strains, more countries have implemented mass campaigns and routine immunisation programmes to control outbreaks with MenACWY vaccines and can assess impact through disease incidence and carriage studies. The current evidence indicates that MenACWY (MenQuadfi) has similar or superior immunogenicity to other MenACWY vaccines; real-world effectiveness data is limited to date as it was first licensed in 2020.

Several phase II and III clinical trials have assessed the immunogenicity of the MenACWY vaccine, MenQuadfi. These studies have included healthy vaccine-naive toddlers aged from 12 months; vaccine-naïve older children and adolescents; booster doses in toddlers, children and adolescents following prior MenACWY or MenC vaccination; given concurrently with routine vaccines (DTaP-IPV-HepB/Hib, MMR, VV, PCV13, Tdap and HPV); and in adults aged over 56 years.[24] In all studies, robust antibody responses were observed in all groups, immunogenicity was non-inferior to comparator vaccines and booster responses were observed.

Bactericidal antibody responses in adults (aged 18-55 years) were two to six times greater in those vaccinated with MenQuadfi, compared those vaccinated with diphtheria-toxoid conjugated MenACWY (Menactra), and a higher proportion of participants had a positive seroresponse.[25]

One clinical trial observed lower antibody responses to FHA, PRN and FIM2/3 pertussis antigens but not pertussis toxin, when MenACWY was given concurrently with Tdap and HPV in adolescents compared with without MenACWY.[26] The clinical relevance is unknown and has been observed with other MenACWY vaccines.[24] No interference was documented with other vaccines. There is no published data to date on effectiveness or use in immunocompromised individuals.

The other MenACWY-T vaccine (Nimenrix) is registered in New Zealand for individuals from aged 6 weeks. Clinical trials showed that the vaccine elicited bactericidal antibodies against all four groups from age 2 months with acceptable reactogenicity and safety profile.[27]

There is no published data on effectiveness in older adults for these vaccines.

Meningococcal group C conjugate vaccine

Meningococcal C conjugate vaccines were used successfully in national immunisation and mass vaccination programmes from 1999 in the UK, resulting in almost complete elimination of group C disease.[28] A targeted immunisation campaign during an epidemic in Salvador, Brazil demonstrated MenC vaccination to be 98 percent effective against group C disease in young children.[29] A booster dose in the second year of life was indicated in the UK for sustained protection.[30] The greatest impact from meningococcal immunisation campaigns was obtained through herd immunity and a reduction in transmission was observed across all age groups, including in unvaccinated adults, where catch-up programmes in adolescents were implemented.[31, 32]

With the emergence of group W and group Y meningococci, MenC has largely been replaced by MenACWY vaccines on national programmes for infants and adolescents.

Transport according to the National Standards for Vaccine Storage and Transportation for Immunisation Providers 2017 (2nd edition).

Store at +2°C to +8°C. MenACWY vaccines and MenB should be protected from light. Do not freeze.

Reconstitution

The MenACWY vaccine, Nimenrix, must be reconstituted with the supplied diluent and used as soon as possible. The other meningococcal vaccines are fully liquid formulations and do not require reconstitution.

Meningococcal group B recombinant vaccine (MenB)

Each MenB (Bexsero) dose is 0.5 ml, administered by intramuscular injection (see section 2.2.3).

• For infants aged 8 weeks to 11 months, two doses are given with a minimum of eight weeks between doses, with a booster given at least six months after the second dose, from age 12 months.
• For toddlers aged 12­–23 months (at time of first dose) a primary course of two doses is given at least eight weeks apart. A booster dose is recommended from 12 to 23 months after dose two.
• For children aged from 2 years (at time of first dose) and adults, two doses are given at least eight weeks apart (see section 13.5.1 for reduced spacing). (Note: the safety and efficacy in individuals aged over 50 years have not been established, but no safety concerns are expected.)

Generally, the need for booster doses from the age 2 years or older at the time of their first dose has not been established. A booster dose can be considered for individuals at continued risk of exposure to meningococcal disease. Booster doses are funded five-yearly for some high-risk individuals (see Table 13.6).

MenB can be administered concurrently with other scheduled vaccines, in separate syringes and at separate sites (see section 2.2.7).

See section 13.5.1 for recommendations around antipyretic prophylaxis use with delivery in children aged under 2 years.

Quadrivalent meningococcal conjugate vaccines (MenACWY)

Each MenACWY dose is 0.5 mL, administered by intramuscular injection (see section 2.2.3).

MenACWY and MenC vaccines can be concurrently administered with other vaccines in separate syringes and at separate sites.

MenQuadfi

MenQuadfi is given as a single dose to individuals aged 12 months and over. See Table 13.6 for schedules and dosing for certain special groups.

A single booster dose may be given to adolescent and adults who have been primed with another MenACWY vaccine at least 4 years previously. There is currently no data available to indicate the need for or timing of a booster dose.

Nimenrix 

MenACWY-T (Nimenrix) is available (not funded) in New Zealand for individuals from age 6 weeks.

• For infants aged under 12 months, two doses are given eight weeks apart, plus a booster from age 12 months at least six months after second dose.
• Healthy infants aged 6 months to under 12 months, who are not immunocompromised, can be given one dose instead of two primary doses, plus a booster from age 12 months, at least eight weeks later.
• For adults and children from age 12 months, one dose is given.
• Booster doses may be indicated in some individuals.

Meningococcal group C conjugate vaccine (MenC)

Each MenC (NeisVac-C) dose is 0.5 mL, administered by intramuscular injection (see section 2.2.3). See Table 13.6 for schedules for at-risk individuals.

For infants aged under 12 months, two doses are given at least eight weeks apart, with the first dose given not earlier than age 6 weeks. One dose of MenACWY is recommended in the second year of life at age 12 months or over.

In view of the New Zealand epidemiology, a quadrivalent (MenACWY) vaccine would be preferable, to obtain broader meningococcal protection.

A primary course of MenB is recommended and funded for all children at ages 3 months, 5 months and a booster given at age 12 months. In an alternative approved schedule, MenB can be given at ages 2 months (ie, approved from 8 weeks) and 4 months with a booster at age 12 months; this would be outside the standard scheduled immunisation visits. Do not delay the 6-week vaccination event for the other Schedule vaccines.

For children at high risk of meningococcal disease aged younger than 8 weeks, to align with the routine schedule visit, MenB can be given at ages 6 weeks and 3 months. This is off-label use and requires a prescription for both events. No prescription is required if given as per the alternative schedule at ages 2 and 4 months.

A catch-up programme of MenB is funded for children aged 13 months to 59 months until 31 August 2025. All children eligible for meningococcal B catch-up should be vaccinated at the earliest opportunity. Give two doses 8 weeks apart. For children those aged 12 to under 24 months at time of their first dose, a further dose can be given from 12 to 24 months after second dose. If MenB is started before the age 5 years, then the funded course can be completed. There is now some flexibility for children eligible for catch-up who then turn 5 years old before receiving their first MenB dose. These children can still be offered the funded vaccine course; this should be given at the earliest opportunity and before the end of the catch-up period.

As an antipyretic, prophylactic paracetamol is recommended to be given up to 30 minutes prior to or immediately after MenB vaccination and give up to two further doses four to six hours apart for children aged under 2 years. Ibuprofen may be given as an alternative to paracetamol six to eight hourly (see section 13.7.1).

Meningococcal vaccines are funded in special circumstances, as described in the shaded section of Table ‎13.5; Table ‎13.6 shows the recommended dosing schedules.

See sections 4.3, 4.4 and 4.5 for more information about vaccination of special groups, including recommended immunisation schedules for high-risk individuals with certain medical conditions.

The meningococcal vaccines are recommended (but not funded) for other individuals at risk, as described in non-shaded rows in Table 13.5.

Before travel

There are areas of the world where the risk of meningococcal disease is increased. Nevertheless, the risk to travellers to the developing world has been estimated as being less than one in a million per month. Recurrent epidemics of meningococcal disease occur in the sub-Saharan ‘meningitis belt’, from Senegal in the west to Ethiopia in the east, usually during the dry season (December to June). Epidemics are occasionally identified in other parts of the world, including in Europe and the Americas. Generally, countries outside of Africa experience smaller outbreaks, but case-fatality rates can be high.

The preferred vaccines (MenACWY and/or MenB) for travel would be based on the epidemiology of the country. For website sources for information about meningococcal vaccines for travellers, see the WHO website. Quadrivalent meningococcal vaccine is a requirement for pilgrims to the Hajj.

Before moving into communal living situations

MenACWY and MenB are recommended and funded from age 13–25 years inclusively for individuals who will be living in communal accommodation within the next three months, or who are in their first year of living in communal accommodation (specifically, boarding school hostels, tertiary education halls of residence, military barracks, youth justice residences or prisons) as they are likely to be at higher risk of acquiring meningococcal infection.

Non-high-risk children and adolescents may be offered meningococcal vaccines. These vaccines are only funded for certain groups (see Table 13.4). Table ‎13.7 suggests the most appropriate ages for this, reflecting the known ages of increased risk. The predominant meningococcal strains in New Zealand in childhood are B, W and Y. With the current New Zealand epidemiology, neither MenACWY nor MenB give protection across all prevailing meningococcal groups and both types of vaccine are recommended. For those who are likely to travel, the broadest protection is preferable because of the differing serotype patterns between countries.

There are no reports of any adverse effects among pregnant women who have been vaccinated during pregnancy.[33] Meningococcal vaccines may be given in pregnancy and to those who are lactating, if indicated.[34, 35]

Meningococcal conjugate vaccines, MenC, MenACWY and MenB are funded for vaccination or re-vaccination of eligible individuals, as follows. See also section 4.3.

Meningococcal conjugate vaccines

For MenC (age 11 months and under) and MenACWY (age 12 months and over), up to three doses plus booster doses (as appropriate) are funded for individuals:

• pre- or post-splenectomy
• pre- or post-solid organ transplantation
• with functional asplenia
• with complement deficiency (acquired or inherited)
• who are HIV-positive.

Two doses are funded for individuals:

• post-haematopoietic stem cell transplantation
• prior to planned and following immunosuppression for longer than 28 days.

Recombinant meningococcal B vaccine, MenB

• Age under 12 months – up to three doses, plus booster after age 12 months and every five years (as appropriate)
• Age from 12 – 23 months – up to two doses plus booster given 12 to 23 months after second dose, and booster every five years (as appropriate)
• Age from 2 years – up to two doses plus a booster every five years (as appropriate)

Primary vaccination plus booster doses funded individuals:

• pre- or post-splenectomy
• pre- or post-solid organ transplantation
• with functional or anatomic asplenia
• with complement deficiency (acquired or inherited)
• who are HIV-positive.

Two primary doses are funded for individuals aged from 12 months:

• post-haematopoietic stem cell transplantation
• prior to planned and following immunosuppression for longer than 28 days.

There is an increased risk of fever and medically attended fever-related events, such as sepsis screening and febrile seizures associated with MenB in some children age under 2 years.[4, 36, 37, 38, 39] These events peaked at six hours post-vaccination and generally subsided by day 3. Fever of at least 38°C was observed in 80 percent of infants who received MenB and routine vaccines concomitantly, and 71 percent who had MenB and routine vaccines separately, compared with 51 percent who receive routine vaccines only.[40, 41] Paracetamol was show to reduce the incidence of fever. Prophylaxic paracetamol is recommended from 30 minutes prior to or immediately after vaccination, then two further doses can be given four to six hours apart for children aged under 2 years. Some infants will still develop a fever and/or injection-site pain even though they have received paracetamol doses.[42]

In clinical trials, most infants and young children had at least one solicited adverse reaction (84–97 percent)[41], including injection-site tenderness and irritability. Adolescents and adults may experience localised pain, nausea, myalgia, malaise, mild fever and headache.

Potential adverse reactions after meningococcal conjugate vaccines include localised injection-site pain, irritability, headache, malaise and fatigue.[27, 43] The safety profile of all the MenACWY vaccines are very similar.[27, 33, 44] In infants, unusual crying, irritability, drowsiness and vomiting have been reported in clinical trials.[25, 45] Fever is reported by 2–5 percent of adolescents and less than 10 percent of infants who receive MenACWY. Concurrent administration with routine vaccines did not increase solicited systemic responses in young children (when given with PCV13) but was slightly increased in adolescents (with Tdap and HPV) during clinical trials of MenQuadfi.[25, 44, 45]

Guillain–Barré syndrome

There is no evidence of an association between meningococcal conjugate vaccines and GBS. An early report in the US of a suspected temporal association between MenACWY (Menactra) and GBS was followed by a large retrospective cohort study in the US that found no evidence of an increased risk of GBS following administration of MenACWY.[34, 46] If indicated, meningococcal conjugate vaccines may be administered to individuals with a history of GBS.[47]

A Cochrane Review assessed the safety of MenC against group C disease.[48] MenC vaccines were shown to have an excellent safety profile in infants. The events more frequently reported in infants were fever (1–5 percent), irritability (38–67 percent), crying more than expected (1–13 percent), redness at the site of vaccination (6–97 percent), tenderness at the site of vaccination (11–13 percent) and swelling at the site of vaccination (6–42 percent). Anaphylaxis was reported at a rate of one per 500,000 doses distributed.[4]

A contact is anyone who has had unprotected contact with upper respiratory tract or respiratory droplets from the case during the seven days before onset of illness to 24 hours after onset of effective treatment.[49] Contacts at particular risk include:

• those sleeping at least one night in the same household, dormitory, military barrack or student hostel bunkroom (not residents of nursing or residential homes who sleep in separate rooms) as the case, or who have been in a seat adjacent to the case in a plane, bus or train for more than eight hours
• health care workers who have had intensive unprotected contact (not wearing a mask) with a case during intubation, resuscitation or close examination of the oropharynx
• exchange of upper respiratory tract secretions, including intimate kissing
• other contacts as determined by the medical officer of health on a case-by-case basis, such as children and staff attending an early childhood service.

Prophylaxis is not routinely recommended for health care personnel unless there has been intimate contact with oral secretions (eg, performing mouth-to-mouth resuscitation or suctioning of the case before antibiotic therapy has started).

Recommended antibiotics

The recommended antibiotics are rifampicin, ceftriaxone or ciprofloxacin, preferably given within 24 hours of initial diagnosis, but prophylaxis is recommended up to 14 days after diagnosis of illness.

Rifampicin

The recommended dose of rifampicin is 10 mg/kg (maximum dose 600 mg) every 12 hours for two days. For infants aged under 4 weeks, the recommended dose is 5 mg/kg every 12 hours for two days.

Rifampicin should be avoided for pregnant or lactating women.

Ceftriaxone

A single dose of intramuscular ceftriaxone (125 mg for children aged under 12 years and 250 mg for older children and adults) has been found to have an efficacy equal to that of rifampicin in eradicating the meningococcal group A carrier state. Ceftriaxone is the drug of choice in a pregnant woman because rifampicin is not recommended later in pregnancy. Ceftriaxone may be reconstituted with lignocaine (according to the manufacturer’s instructions) to reduce the pain of injection. A New Zealand study demonstrated that ceftriaxone and rifampicin were equivalent in terms of eliminating nasopharyngeal carriage of N. meningitidis group B.[50]

Do not use in infants under aged under 4 weeks.

Ciprofloxacin

Ciprofloxacin given as a single oral dose of 500 mg or 750 mg is also effective at eradicating carriage. This is the preferred prophylaxis for women on the oral contraceptive pill and for prophylaxis of large groups.[49]

Ciprofloxacin is not generally recommended for pregnant and lactating women or for children aged under 18 years.[51] Consult the manufacturer’s data sheet for appropriate use and dosage of ciprofloxacin in children.

Use of meningococcal vaccines for close contacts

Close contacts of cases of any group (including group A, B, C, W or Y) meningococcal disease may be offered both MenB and MenACWY (or MenC if aged under 9 months) meningococcal vaccines (see section ‎13.5).

See below for the use of the vaccines for the control of outbreaks, as initiated by the local public health service.

When there is an outbreak of meningococcal disease of a specific vaccine group, an immunisation programme may be recommended and funded for a defined population. The local medical officer of health will determine the necessary action in discussion with Health NZ | Te Whatu Ora.

For more details on control measures, refer to the ‘Neisseria meningitidis invasive disease’ chapter of the Communicable Disease Control Manual .

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